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Zhang Q, Xu Z, Liu W, Cheng Z, Ding Y, Xie Y, Yan S. Gastrodin promotes ferroptosis in CRC cells by inhibiting SKP2 to reduce NCOA4 ubiquitination. Tissue Cell 2025; 95:102793. [PMID: 40048831 DOI: 10.1016/j.tice.2025.102793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2024] [Revised: 01/28/2025] [Accepted: 02/10/2025] [Indexed: 05/15/2025]
Abstract
BACKGROUND Gastrodin, an important component of traditional Chinese medicine, is gaining interest because of its anti-tumor effects. Ferroptosis is a new mode of cell death, which has emerged as a promising target for colorectal cancer (CRC) treatment. This research investigates the action mechanism of gastrodin on the process of CRC by inducing ferroptosis. METHODS The mRNA and protein levels were measured via qRT-PCR and western blot. Cell viability was assessed by CCK-8 assay. The cell proliferation was examined using colony formation assay. Live-Dead cell staining was evaluated by Calcein-AM/PI staining. The effect of ferroptosis was evaluated by detecting the levels of reactive oxygen species (ROS), intracellular total iron, ferrous iron (Fe2 +), malondialdehyde (MDA), glutathione (GSH) by kits, as well as the expressions of subunit solute carrier family 7 member 11 (SLC7A11), glutathione peroxidase 4 (GPX4), ferritin light chain (FTL) and acyl-CoA synthetase long chain family member 4 (ACSL4) by western blot. Co-immunoprecipitation (Co-IP) assay was applied to analyze the binding relationship between S-phase kinase-associated protein 2 (SKP2) and nuclear receptor coactivator 4 (NCOA4). RESULTS Gastrodin could induce ferroptosis in CRC cells. SKP2 ameliorated gastrodin induced ferroptosis in CRC cells. Besides, SKP2 mediated NCOA4 degradation by ubiquitination. SKP2 was involved in ferroptosis of CRC cells by regulating NCOA4. Gastrodin induced ferroptosis in CRC cells via SKP2/NCOA4 axis. CONCLUSION Gastrodin repressed SKP2 expression, deactivated NCOA4 ubiquitination thus elevated NCOA4 expression, and promoted ferroptosis in CRC cells.
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Affiliation(s)
- Qiao Zhang
- Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
| | - Zhijie Xu
- Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
| | - Wanying Liu
- Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
| | - Zhidong Cheng
- Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
| | - Yating Ding
- Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
| | - Yafeng Xie
- Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
| | - Shengyu Yan
- Department of Proctology, the Second Affiliated Hospital, University of South China, Hengyang, 421001, Hunan, China; Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
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2
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Xiao Z, Puré E. The fibroinflammatory response in cancer. Nat Rev Cancer 2025; 25:399-425. [PMID: 40097577 DOI: 10.1038/s41568-025-00798-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/06/2025] [Indexed: 03/19/2025]
Abstract
Fibroinflammation refers to the highly integrated fibrogenic and inflammatory responses mediated by the concerted function of fibroblasts and innate immune cells in response to tissue perturbation. This process underlies the desmoplastic remodelling of the tumour microenvironment and thus plays an important role in tumour initiation, growth and metastasis. More specifically, fibroinflammation alters the biochemical and biomechanical signalling in malignant cells to promote their proliferation and survival and further supports an immunosuppressive microenvironment by polarizing the immune status of tumours. Additionally, the presence of fibroinflammation is often associated with therapeutic resistance. As such, there is increasing interest in targeting this process to normalize the tumour microenvironment and thus enhance the treatment of solid tumours. Herein, we review advances made in unravelling the complexity of cancer-associated fibroinflammation that can inform the rational design of therapies targeting this.
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Affiliation(s)
- Zebin Xiao
- Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA, USA
| | - Ellen Puré
- Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA, USA.
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3
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Fish JE, Eleti S, Power N, Nandra G. Imaging of young-onset colorectal cancer: what the radiologist needs to know. Abdom Radiol (NY) 2025:10.1007/s00261-025-04976-y. [PMID: 40382481 DOI: 10.1007/s00261-025-04976-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Revised: 04/19/2025] [Accepted: 04/27/2025] [Indexed: 05/20/2025]
Abstract
Young-onset colorectal cancer (YOCRC) refers to colorectal cancer diagnosed in individuals under the age of 50. Whilst the overall incidence of colorectal cancer is decreasing, YOCRC cases are increasing and now accounts for up to 10% of all colorectal cancers. YOCRC more frequently presents with acute symptoms, where radiologists play an important role in identifying malignancy and distinguishing it from benign colonic pathologies. Risk factors associated with YOCRC, such as inflammatory bowel disease and hereditary syndromes, may exhibit specific imaging manifestations. In addition, YOCRC is frequently associated with a mucinous histopathological subtype which may be identifiable based on the presence of specific imaging features. Given their younger age, these patients are more likely to undergo aggressive treatment and complex surgical interventions. Specific considerations such as fertility preserving surgical techniques must be factored in when managing these patients. As the incidence of YOCRC increases, guidance for colonoscopy screening protocols may need revision. This includes evaluating the role of ionising imaging techniques in both diagnosing and follow-up to balance early detection and minimising radiation exposure in this younger patient population.
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Affiliation(s)
| | - Saigeet Eleti
- Imaging Department, Royal London Hospital, London, UK
| | - Niall Power
- Imaging Department, Royal London Hospital, London, UK
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4
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Vande Perre P, Al Saati A, Cabarrou B, Plenecassagnes J, Gilhodes J, Monselet N, Lignon N, Filleron T, Villarzel C, Gourdain L, Selves J, Martinez M, Chipoulet E, Collet G, Mallet L, Bonnet D, Guimbaud R, Toulas C. Germline Sequencing of Familial and Sporadic Early-Onset Colorectal Cancer: A Novel Pattern of Genes. Int J Mol Sci 2025; 26:4672. [PMID: 40429818 PMCID: PMC12111735 DOI: 10.3390/ijms26104672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2025] [Revised: 05/02/2025] [Accepted: 05/08/2025] [Indexed: 05/29/2025] Open
Abstract
The majority of early-onset colorectal cancers (EOCRCs) are not substantiated by germline variants in the main CRC predisposition genes (the "DIGE" panel). To identify potentially novel EOCRC-specific predisposition genes, we analyzed 585 cancer pathway genes in an EOCRC patient cohort (n = 87, diagnosis ≤ 40 years, DIGE-), and compared their variant spectrum to the GnomAD cancer-free database. We identified high-impact variants (HVs) in 15 genes significantly over-represented in EOCRC. Among the 32 unrelated patients with a CRC family history (i.e., with a potentially dominant transmission pattern), 9 presented HVs in ten genes, four of which had a DNA repair function. We subsequently sequenced these 15 genes in a cohort of 82 late-onset CRCs (diagnosis ≥ 50 years, DIGE-) and found variants in 11 of these genes to be specific to EOCRC. We then screened these 11 genes in our patient database (n = 6482), which only contained 2% of EOCRCs (DIGE-), and identified two other EOCRC cases diagnosed after our cohort constitution, with HVs in RECQL4 and NUTM1. Altogether, we found that 37.5% and 18.75% of patients carrying heterozygous NUTM1 and RECQL4 HVs, respectively, in our database were diagnosed with EOCRC. Our work has identified a pattern of germline variants not previously associated with EOCRC.
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Affiliation(s)
- Pierre Vande Perre
- Oncogenetics Laboratory, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (P.V.P.); (A.A.S.)
- DIAD Team, INSERM U1037, Centre de Recherches en Cancérologie de Toulouse, 31100 Toulouse, France
- Oncogenetics Department, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (N.L.); (E.C.); (D.B.); (R.G.)
| | - Ayman Al Saati
- Oncogenetics Laboratory, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (P.V.P.); (A.A.S.)
- DIAD Team, INSERM U1037, Centre de Recherches en Cancérologie de Toulouse, 31100 Toulouse, France
- Faculté de Santé, Université de Toulouse, 31400 Toulouse, France
| | - Bastien Cabarrou
- Biostatistics & Health Data Science Unit, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (B.C.); (T.F.)
| | - Julien Plenecassagnes
- Bioinformatic Department, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (J.P.); (L.M.)
| | - Julia Gilhodes
- Biostatistics & Health Data Science Unit, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (B.C.); (T.F.)
| | - Nils Monselet
- Biostatistics & Health Data Science Unit, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (B.C.); (T.F.)
| | - Norbert Lignon
- Oncogenetics Department, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (N.L.); (E.C.); (D.B.); (R.G.)
| | - Thomas Filleron
- Biostatistics & Health Data Science Unit, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (B.C.); (T.F.)
| | - Carine Villarzel
- Oncogenetics Laboratory, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (P.V.P.); (A.A.S.)
| | - Laure Gourdain
- Oncogenetics Laboratory, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (P.V.P.); (A.A.S.)
| | - Janick Selves
- Pathology Laboratory, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France;
| | | | - Edith Chipoulet
- Oncogenetics Department, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (N.L.); (E.C.); (D.B.); (R.G.)
- CHU de Toulouse, 31059 Toulouse, France
| | - Gaëlle Collet
- Oncogenetics Department, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (N.L.); (E.C.); (D.B.); (R.G.)
- CHU de Toulouse, 31059 Toulouse, France
| | - Ludovic Mallet
- Bioinformatic Department, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (J.P.); (L.M.)
| | - Delphine Bonnet
- Oncogenetics Department, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (N.L.); (E.C.); (D.B.); (R.G.)
- CHU de Toulouse, 31059 Toulouse, France
| | - Rosine Guimbaud
- Oncogenetics Department, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (N.L.); (E.C.); (D.B.); (R.G.)
- Faculté de Santé, Université de Toulouse, 31400 Toulouse, France
- CHU de Toulouse, 31059 Toulouse, France
| | - Christine Toulas
- Oncogenetics Laboratory, Oncopole Claudius Regaud, IUCT-Oncopole, 31059 Toulouse, France; (P.V.P.); (A.A.S.)
- DIAD Team, INSERM U1037, Centre de Recherches en Cancérologie de Toulouse, 31100 Toulouse, France
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Samuel SM, Varghese E, Büsselberg D. Complexity of insulin resistance in early-onset colorectal cancer. Cancer Cell 2025; 43:797-802. [PMID: 40250447 DOI: 10.1016/j.ccell.2025.03.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 02/19/2025] [Accepted: 03/28/2025] [Indexed: 04/20/2025]
Abstract
Early-life exposure to lifestyle-associated metabolic alterations could be a key contributor to early-onset colorectal cancer (EOCRC). Notably, insulin resistance (InsR)-linked hyperinsulinemia, elevated levels of insulin-like growth factors, and chronic inflammation could trigger EOCRC by modulating gene expression/pathways that support carcinogenesis/anti-apoptosis. Here, we discuss how InsR could be the trigger that offsets metabolic homeostasis in young individuals, leading to EOCRC. Furthermore, we emphasize the need for lifestyle interventions, early detection, and targeted therapeutic interventions to mitigate this growing health concern.
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Affiliation(s)
- Samson Mathews Samuel
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Medbay, Education City, Qatar Foundation, 24144 Doha, Qatar.
| | - Elizabeth Varghese
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Medbay, Education City, Qatar Foundation, 24144 Doha, Qatar
| | - Dietrich Büsselberg
- Department of Physiology and Biophysics, Weill Cornell Medicine-Qatar, Medbay, Education City, Qatar Foundation, 24144 Doha, Qatar.
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6
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Peng C, Littman D, Masri L, Sherman S, Makarov DV, Becker DJ. Fertility counseling in early-onset colorectal cancer and the impact of patient characteristics. Support Care Cancer 2025; 33:466. [PMID: 40347312 DOI: 10.1007/s00520-025-09517-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Accepted: 05/02/2025] [Indexed: 05/12/2025]
Abstract
PURPOSE This study evaluated how frequently patients with early onset colorectal cancer received fertility counseling and whether patient characteristics affected the likelihood of receiving such counseling. METHODS We conducted a single-center retrospective review of all new patients seen by medical oncology for colorectal cancer who were age 55 years or younger for men and 50 years or younger for women. Associations between patient demographics and clinical characteristics with receipt of fertility counseling were explored using univariate analyses and multivariable logistical regression analyses. RESULTS A total of 194 patients were included, of whom 15.5% received fertility counseling. Using multivariate analysis, we found that age < 40 (OR 15.587, p < 0.0001, 95% CI 4.841-50.191) and female sex (OR 3.979, p = 0.0292, 95% CI 1.150-13.770) were correlated with increased likelihood of fertility counseling. Patients living in areas of higher household income were more likely to receive fertility counseling, with a statistically significant difference between the 3rd and 1st quartiles of income (p = 0.0369, 95% CI 1.161-115.940). CONCLUSION A majority of patients with EOCRC did not receive fertility counseling despite the known toxicities of CRC treatment modalities on fertility. Older age, male sex, and residence in areas of lower income were associated with decreased likelihood of receiving fertility counseling.
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Affiliation(s)
| | | | - Lena Masri
- VA New York Harbor Health Care, New York, NY, USA
| | - Scott Sherman
- NYU Grossman School of Medicine, New York, NY, USA
- VA New York Harbor Health Care, New York, NY, USA
| | - Danil V Makarov
- NYU Grossman School of Medicine, New York, NY, USA
- VA New York Harbor Health Care, New York, NY, USA
| | - Daniel J Becker
- NYU Grossman School of Medicine, New York, NY, USA.
- VA New York Harbor Health Care, New York, NY, USA.
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7
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Zhang X, Fan H, Han S, Zhang T, Sun Y, Yang L, Li W. Global burden of colon and rectal cancer and attributable risk factors in 204 countries and territories from 1990 to 2021. BMC Gastroenterol 2025; 25:332. [PMID: 40316922 PMCID: PMC12048922 DOI: 10.1186/s12876-025-03948-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2025] [Accepted: 04/28/2025] [Indexed: 05/04/2025] Open
Abstract
OBJECTIVE Colon and rectal cancers (CRCs) are among the most common malignancies worldwide. While previous studies have examined the disease burden and risk factors of CRC at regional levels, they lack the granularity needed for country-specific policy development. Using updated data from the Global Burden of Disease (GBD) 2021 study, this research explores the national-level spatial distribution of CRC burdens linked to key risk factors and analyzes temporal trends in their contributions. The findings aim to support the formulation of precise public health policies to effectively reduce CRC incidence. METHODS Based on data from the GBD study 2021, we examined CRC-related incidence, prevalence, mortality, disability-adjusted life years (DALYs), and associated risk factors. Age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and DALY rate (ASDR) were obtained and analyzed from 1990 to 2021. We used regression analysis and stratification across the four World Bank regions to assess geographical variations and the effect of economic development levels. We further assessed the contribution of various risk factors to CRC-related deaths and DALYs, while analyzing the distribution and temporal trends of the top three contributing risk factors. RESULTS On a global scale, the ASDR for CRC declined from 357.33 per 100,000 in 1990 to 283.24 per 100,000 in 2021 (95% confidence interval [CI]: -0.82 to -0.64). In 2021, the regions classified by the World Bank as high income exhibited the highest ASDR in 2021, at 347.35 per 100,000, while the lower-middle-income regions reported the lowest ASDR, at 179.48 per 100,000. During this period, the global ASMR fell from 15.56 to 12.40 per 100,000, while the ASIR rose from 24.04 to 25.60 per 100,000. However, these trends were not consistent across different World Bank income regions. Key risk factors contributing to CRC included high red meat consumption, obesity, insufficient calcium intake, and alcohol consumption, with variations observed among the World Bank income groups. CONCLUSION Although the global burden of colorectal cancer (CRC) has declined from 1990 to 2021, particularly in high-income regions, the incidence rate continues to rise. The increase is more pronounced among individuals aged 50 years and older, who also bear a higher absolute incidence than younger populations. High red meat consumption, high body mass index (BMI), and low calcium intake remain the leading global risk factors for CRC. Effective weight management and the promotion of healthy lifestyles are essential strategies for reducing CRC risk across sexes, while smoking and alcohol control are particularly critical for alleviating the burden among males.
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Affiliation(s)
- Xuyuan Zhang
- School of Clinical Medicine, Bengbu Medical University, Bengbu, 233030, China
| | - Haoyu Fan
- School of Clinical Medicine, Bengbu Medical University, Bengbu, 233030, China
| | - Sen Han
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Oncology II, Peking University Cancer Hospital and Institute, Beijing, 100142, China
| | - Ting Zhang
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Yanxia Sun
- School of Population Medicine and Public Health, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
| | - Liuyang Yang
- Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.
- School of Data Science, Fudan University, Shanghai, China.
| | - Wenliang Li
- Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China
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Benvenisti H, Assaf D, Mor E, Mor-Hadar D, Kepenekian V, Flamey N, Yang R, Zippel D, Ben-Yaacov A, Li Y, Moran B, Glehen O, Nissan A. Successful pregnancy following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with peritoneal malignancies. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2025; 51:109725. [PMID: 40043663 DOI: 10.1016/j.ejso.2025.109725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2024] [Revised: 02/18/2025] [Accepted: 02/23/2025] [Indexed: 05/13/2025]
Abstract
BACKGROUND Cytoreductive surgery (CRS) with Hyperthermic Intra-peritoneal Chemotherapy (HIPEC) has become a successful, potentially curative, treatment option for peritoneal surface malignancies (PSM). CRS and HIPEC (CRS/HIPEC) are performed with curative intent for several intra-peritoneal pathologies. An increasing number of patients with PSM are diagnosed at a relatively young age. Given the long-term survival in some patients following CRS/HIPEC, the reproductive health of patients in this age group requires consideration. METHODS Surgical oncology teams participating in the Peritoneal Surface Oncology Group International (PSOGI) were offered the opportunity to share their experience and data regarding the obstetric outcomes of female patients who had undergone CRS/HIPEC. RESULTS Nineteen (19) patients were reported to have had a baby following CRS/HIPEC. The median interval between CRS/HIPEC and pregnancy was 37 months, and 16 patients had a normal vaginal delivery. All of the newborns were healthy, without medical issues attributed to CRS or HIPEC chemotherapy. Overall, 89 % of mothers had no evidence of disease at their last follow-up. CONCLUSION Successful pregnancies following CRS/HIPEC are seldom reported in the literature, and fertility preservation is not uniformly discussed. Data from this international collaboration highlights the reproductive potential in patients with PSM following CRS/HIPEC and the value of pre-operative obstetric and fertility advice and management to achieve that end.
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Affiliation(s)
- Haggai Benvenisti
- Department of General Surgery, The Chaim Sheba Medical Center, Ramat Gan, Israel.
| | - Dan Assaf
- Department of General Surgery, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Eyal Mor
- Department of General Surgery, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Danielle Mor-Hadar
- Department of Obstetrics& Gynecology, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Vahan Kepenekian
- Department of Oncologic Surgery, Centre Hospitalier Lyon Sud, Pierre Benite, and CICLY EMR 3738, Lyon 1 University, Lyon, France
| | - Nicolas Flamey
- Peritoneal Malignancy Institute, Basinsgtoke, North Hampshire Hospital Foundation Trust, Basingstoke, Hampshire, RG24 9NA, UK
| | - Rui Yang
- Department of Surgical Oncology, Beijing Tsinghua Changgung Hospital, Affiliated to Tsinghua University, Beijing, China
| | - Douglas Zippel
- Department of General Surgery, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Almog Ben-Yaacov
- Department of General Surgery, The Chaim Sheba Medical Center, Ramat Gan, Israel
| | - Yan Li
- Department of Surgical Oncology, Beijing Tsinghua Changgung Hospital, Affiliated to Tsinghua University, Beijing, China
| | - Brendan Moran
- Peritoneal Malignancy Institute, Basinsgtoke, North Hampshire Hospital Foundation Trust, Basingstoke, Hampshire, RG24 9NA, UK
| | - Olivier Glehen
- Department of Oncologic Surgery, Centre Hospitalier Lyon Sud, Pierre Benite, and CICLY EMR 3738, Lyon 1 University, Lyon, France
| | - Aviram Nissan
- Department of General Surgery, The Chaim Sheba Medical Center, Ramat Gan, Israel; Department of Surgery, Ziv Medical Center, Affiliated with Bar-Ilan University School of Medicine, Tzfat, Israel
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Zhan Z, Chen B, Lin W, Chen X, Huang R, Yang C, Guo Z. Rising Burden of Colon and Rectum Cancer in China: An Analysis of Trends, Gender Disparities, and Projections to 2030. Ann Surg Oncol 2025; 32:3361-3371. [PMID: 39836276 DOI: 10.1245/s10434-025-16905-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Accepted: 01/06/2025] [Indexed: 01/22/2025]
Abstract
BACKGROUND Colon and rectum cancer (CRC) is a major health burden in China, with notable gender disparities. This study was designed to analyze trends in CRC incidence, prevalence, and mortality from 1990 to 2021 and to project future trends. METHODS Using data from the Global Burden of Disease (GBD) Study 2021, we examined CRC burden in China, including incidence, prevalence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs). Joinpoint regression, Bayesian age-period-cohort (BAPC) models, and age-period-cohort (APC) analysis identified trends and projected incidence up to 2030. RESULTS In 2021, CRC incidence was 658,321 cases, disproportionately affecting males, with an age-standardized incidence rate of 42.24 per 100,000 in males and 21.87 per 100,000 in females. The CRC-related deaths reached 275,129, with higher mortality in males (18.95 per 100,000) than females (9.34 per 100,000). The DALYs totaled 6,848,390 and largely impacted males. Joinpoint analysis showed a persistent increase in incidence and prevalence, especially in younger cohorts, whereas mortality declined slightly but began rising again after 2015. The BAPC analysis projected further incidence growth, particularly in males, through 2030. The APC analysis revealed higher CRC risk among younger cohorts, suggesting increasing early-onset CRC linked to lifestyle risk factors, such as smoking, high alcohol consumption, and diets low in fiber and calcium, with a stronger effect on males. CONCLUSIONS The increase of CRC incidence and prevalence in China, particularly among males, underscores the need for targeted prevention and early detection. Future research should address gender disparities and modifiable lifestyle risks through public health interventions.
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Affiliation(s)
- Zhouwei Zhan
- Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Bijuan Chen
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Wei Lin
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Xiamei Chen
- Department of Operation, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Rui Huang
- Digestive Endoscopy Center, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China
| | - Chunkang Yang
- Department of Gastrointestinal Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.
| | - Zengqing Guo
- Department of Medical Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.
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10
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Zhang J, Wang X, Li Z, Wang Z, Hao X, Li Y, Zhang Y. Comprehensive bioinformatics analysis was used to identify and verify differentially expressed genes in targeted therapy of colon cancer. Sci Rep 2025; 15:14922. [PMID: 40295509 PMCID: PMC12037768 DOI: 10.1038/s41598-025-00011-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 04/24/2025] [Indexed: 04/30/2025] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors. CLCA1 and ZG16 are lowly expressed in CRC, and we wanted to investigate whether they could be prognostic biomarkers for the malignant progression of CRC. 12,195 DEGs and 12,071 DEGs were identified through the GSE39582 dataset and TCGA dataset, and then 50 coexisting genes were selected for further analysis using Venn diagrams. These 50 DEGs were then subjected to GO and KEGG functional enrichment analyses, along with genome-wide GSEA. the first 5 core genes were identified and visualized using Cytoscape through the PPI network. Then the expression of ZG16 and CLCA1 in normal and tumor tissues were analyzed using GSE39582 and TCGA datasets, and correlation analysis, and survival analysis were performed. The expression of ZG16 and CLCA1 in CRC cells was verified by qRT-PCR, and cell proliferation, migration, and invasion abilities were detected by CCK-8, scratch assay, clone formation assay, and Transwell assay. The expression levels of ZG16 and CLCA1 were significantly lower in CRC tissues than in normal tissues. Survival analysis showed that low expression of ZG16 and CLCA1 was associated with poor survival outcomes. Multifactorial analysis showed that low expression of ZG16 and CLCA1 was an independent risk factor affecting tumor prognosis. Cellular experiments showed that cell proliferation, migration, and invasion were inhibited after overexpression of ZG16 and CLCA1. Correlation analysis showed that ZG16 and CLCA1 expression levels were positively correlated and the correlation was statistically significant. GSEA enrichment analysis based on CLCA1-related genes and ZG16-related genes (FDR < 0.25, P < 0.05) revealed that the related genes of both genes were closely related to the GnRH signaling pathway. CLCA1 and ZG16, which are lowly expressed in CRC tissues, are associated with poor prognosis of CRC and may be one of the markers for diagnostic screening and prediction of prognostic outcome in CRC. Meanwhile, CLCA1 and ZG16 may also be new targets for tumor immunotherapy.
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Affiliation(s)
- Jialin Zhang
- Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Research Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, People's Republic of China
| | - Xinyu Wang
- Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Research Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, People's Republic of China
| | - Zhen Li
- Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Research Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, People's Republic of China
| | - Ziqiang Wang
- Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Research Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, People's Republic of China
| | - Xiaona Hao
- Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Research Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, People's Republic of China
| | - Yuyun Li
- Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Research Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, People's Republic of China
| | - Yingjie Zhang
- Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Research Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu, 233030, Anhui, People's Republic of China.
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11
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Manta BA, Ilie AC, Marc F, Nistor D, Mazilu PO, Borza C. Clinical Molecular Immunohistochemistry Mismatch Repair Mutations in Lynch Syndrome in Patients Under 50 Years: A Systematic Review. Biomedicines 2025; 13:1062. [PMID: 40426889 PMCID: PMC12109006 DOI: 10.3390/biomedicines13051062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2025] [Revised: 04/20/2025] [Accepted: 04/25/2025] [Indexed: 05/29/2025] Open
Abstract
Background and Objectives: Lynch syndrome (LS), an autosomal dominant condition arising from germline mutations in mismatch repair (MMR) genes, is a major cause of hereditary early-onset colorectal cancer (CRC). Although patients diagnosed before age 50 represent a critical subgroup where Lynch syndrome might be more prevalent, data on the precise frequency, clinical outcomes, and molecular correlates remain heterogeneous across studies. This systematic review was conducted to (1) estimate the prevalence of MMR deficiency (dMMR) and confirmed LS in patients diagnosed with CRC before the age of 50, and (2) examine immunohistochemistry (IHC) mismatch repair testing patterns and associated molecular findings (BRAF mutations, MLH1 promoter hypermethylation, somatic MMR gene alterations). Methods: Following a predefined search strategy in PubMed, Scopus, and Web of Science, five relevant studies were identified (n = 5). Each study comprised patients younger than 50 who underwent IHC-based tumor screening. Data extraction covered demographic details, number of patients tested, proportion with abnormal IHC, frequency of somatic or germline MMR gene mutations, and method of classification into sporadic dMMR vs. LS. Quality assessment was performed using recommended scales for observational studies. Results: Among 5 studies totaling 960 early-onset CRC patients, the frequency of dMMR CRC ranged from 8.4% to 19.1%. The confirmed prevalence of LS among all young-onset CRC was between 5.0% and 5.9% in three studies but reached 8.9% in another and 5.1% in yet another. Across all studies, the presence of right-sided tumors and histopathological features such as tumor-infiltrating lymphocytes were more common in dMMR cancers. Incorporation of MLH1-promoter hypermethylation and/or BRAF V600E mutation testing aided discrimination of sporadic dMMR CRC from germline LS cases. Conclusions: The prevalence of LS in CRC patients younger than 50 is clinically significant, at approximately 5-9%. Routine IHC-based MMR screening is both feasible and effective for detecting LS in early-onset CRC. Further research is needed to standardize universal testing protocols, delineate the role of additional molecular assays, and ensure comprehensive genetic counseling for at-risk individuals.
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Affiliation(s)
- Bogdan Adrian Manta
- Division of Clinical Practical Skills, Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania;
| | - Adrian Cosmin Ilie
- Department III Functional Sciences, Division of Public Health and Management, “Victor Babes” University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania;
| | - Felicia Marc
- Department of Medical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
| | - Daciana Nistor
- Department of Functional Sciences, Physiology, Centre of Imuno-Physiology and Biotechnologies (CIFBIOTEH), “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
| | - Patricia Octavia Mazilu
- Faculty of Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
| | - Claudia Borza
- Department of Functional Sciences, Discipline of Pathophysiology, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania;
- Centre for Translational Research and Systems Medicine, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
- Centre of Cognitive Research in Pathological Neuro-Psychiatry NEUROPSY-COG, “Victor Babes” University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square 2, 300041 Timisoara, Romania
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12
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Zhang L, Gatlin V, Gupta S, Salinas ML, Romero S, Cai JJ, Chapkin RS, Safe S. Expression of Prooncogenic Nuclear Receptor 4A (NR4A)-Regulated Genes β1-Integrin and G9a Inhibited by Dual NR4A1/2 Ligands. Int J Mol Sci 2025; 26:3909. [PMID: 40332813 PMCID: PMC12028307 DOI: 10.3390/ijms26083909] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Revised: 04/11/2025] [Accepted: 04/14/2025] [Indexed: 05/08/2025] Open
Abstract
Bis-indole-derived compounds including 1,1-bis(3'-indolyl)-1-(3,5-disubstitutedphenyl)methane (DIM-3,5) analogs bind both orphan nuclear receptors 4A1 (NR4A1) and NR4A2, and DIM-3,5 compounds act as dual receptor inverse agonists and inhibit both NR4A1- and NR4A2-regulated responses. Chromatin immunoprecipitation assays show that β1-integrin and the methyltransferase gene G9a are regulated by both NR4A1 and NR4A2 acting as cofactors for Sp1- and Sp4-dependent gene expression. DIM-3,5 treatment results in the loss of one or more of these nuclear factors from the β1-integrin and G9a promoters. Single-cell and RNAseq analyses show that both receptors regulate common (<10%) and unique genes in SW480 colon cancer cells; however, functional enrichment analysis of the differentially expressed genes converges to several common pathways and gene ontology terms.
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MESH Headings
- Humans
- Nuclear Receptor Subfamily 4, Group A, Member 1/metabolism
- Nuclear Receptor Subfamily 4, Group A, Member 1/genetics
- Nuclear Receptor Subfamily 4, Group A, Member 1/agonists
- Integrin beta1/genetics
- Integrin beta1/metabolism
- Cell Line, Tumor
- Ligands
- Histone-Lysine N-Methyltransferase/genetics
- Histone-Lysine N-Methyltransferase/metabolism
- Nuclear Receptor Subfamily 4, Group A, Member 2/metabolism
- Nuclear Receptor Subfamily 4, Group A, Member 2/genetics
- Nuclear Receptor Subfamily 4, Group A, Member 2/agonists
- Histocompatibility Antigens/genetics
- Histocompatibility Antigens/metabolism
- Gene Expression Regulation, Neoplastic/drug effects
- Promoter Regions, Genetic
- Indoles/pharmacology
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Affiliation(s)
- Lei Zhang
- Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA;
| | - Victoria Gatlin
- Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA; (V.G.); (S.G.); (S.R.); (J.J.C.)
- CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX 77843, USA; (M.L.S.); (R.S.C.)
| | - Shreyan Gupta
- Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA; (V.G.); (S.G.); (S.R.); (J.J.C.)
- CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX 77843, USA; (M.L.S.); (R.S.C.)
| | - Michael L. Salinas
- CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX 77843, USA; (M.L.S.); (R.S.C.)
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA
| | - Selim Romero
- Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA; (V.G.); (S.G.); (S.R.); (J.J.C.)
- CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX 77843, USA; (M.L.S.); (R.S.C.)
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA
| | - James J. Cai
- Department of Veterinary Integrative Biosciences, School of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA; (V.G.); (S.G.); (S.R.); (J.J.C.)
- CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX 77843, USA; (M.L.S.); (R.S.C.)
- Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843, USA
| | - Robert S. Chapkin
- CPRIT Single Cell Data Science Core, Texas A&M University, College Station, TX 77843, USA; (M.L.S.); (R.S.C.)
- Department of Nutrition, Texas A&M University, College Station, TX 77843, USA
| | - Stephen Safe
- Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA;
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13
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Li R, Sun X, Yu Z, Li P, Zhao X. Identification of predictors for lymph node metastasis in T2 colorectal cancer: retrospective cohort study from a high-volume hospital. BMC Cancer 2025; 25:700. [PMID: 40234815 PMCID: PMC12001727 DOI: 10.1186/s12885-025-14104-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2024] [Accepted: 04/07/2025] [Indexed: 04/17/2025] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is the most prevalent malignant tumor of the digestive system globally, ranking third in incidence and second in mortality. In previous studies, the rate of lymph node metastasis (LNM) in T2 CRC ranged from 18.0 to 28.0%. We aim to identify T2 CRC patients without LNM and thereby mitigate the complications and potential impact on the quality of life associated with surgery. METHODS In this retrospective study, 787 cases with T2 CRC were selected. The preoperative and postoperative clinicopathological features were retrospectively studied. Univariate analysis and multivariate analysis were performed using binary logistic regression to determine the predictive factor for LNM. Odds ratio (OR) and 95% confidence interval (CI) were conducted. RESULTS 184 (23.4%) patients were diagnosed with LNM, including 144 (78.3%) patients with N1stage and 40 (21.7%) patients with N2 stage. According to univariate analysis and multivariate analysis, poorly differentiated tumors (p = 0.003, OR = 4.405, 95%CI: 1.632-11.893), perineural invasion (p = 0.001, OR = 4.789, 95%CI: 1.958-11.716), and lymphovascular invasion (p = 0.001, OR = 2.779, 95%CI: 1.497-5.159) were independent risk factors of LNM, while male (p = 0.017, OR = 0.652, 95%CI: 0.459-0.926) and elevated preoperative PLR (p = 0.048, OR = 0.996, 95%CI: 0.993-1.000) seemed to be independent protective factors. Larger tumor size did not show significant association with LNM. CONCLUSIONS Approximately three-quarters of T2 CRC patients are likely to avoid unnecessary surgery. Female, poorly differentiated tumors, perineural invasion, and lymphovascular invasion are expected to be used as predictors of LNM in T2 CRC.
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Affiliation(s)
- Rui Li
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, China
| | - Xu Sun
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, China
| | - Zhiyuan Yu
- Medical School of Chinese PLA, Beijing, China
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China
- School of Medicine, Nankai University, Tianjin, China
| | - Peiyu Li
- Medical School of Chinese PLA, Beijing, China.
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
- School of Medicine, Nankai University, Tianjin, China.
| | - Xudong Zhao
- Medical School of Chinese PLA, Beijing, China.
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing, 100853, China.
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14
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Wang K, Wang A, Wang S, Luo Z, Gong Y, Hao X, Yang G, Xu S. The best anthropometric indices to predict colon cancer. BMC Gastroenterol 2025; 25:242. [PMID: 40211175 PMCID: PMC11987457 DOI: 10.1186/s12876-025-03832-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 03/31/2025] [Indexed: 04/12/2025] Open
Abstract
BACKGROUND Colon cancer is one of the most prevalent malignancies globally. Anthropometric data are widely accessible. However, numerous anthropometric indicators exist, and no study has identified the most reliable predictor for colon cancer. This study aims to identify the most effective anthropometric indicators for predicting colon cancer. RESULTS Significant differences were observed in age, race, smoking, diabetes, hypertension, waist circumference, a body shape index (ABSI), Body Roundness Index (BRI), Conicity Index (ConI), Waist-to-Height Ratio(WHtR), and Weight-adjusted Waist Index(WWI) between colon cancer patients and controls (P < 0.05). ABSI (AUC: 0.68, 95% CI: 0.64-0.71), ConI (AUC: 0.68, 95% CI: 0.64-0.71), and WWI (AUC: 0.67, 95% CI: 0.63-0.70) were the most accurate anthropometric indices for predicting colon cancer. ABSI, ConI, and WWI demonstrated a strong correlation. CONCLUSION Analysis of NHANES data (2005-2018) identified ABSI, ConI, and WWI (AUC:0.67-0.68) as optimal anthropometric predictors of colon cancer, emphasizing abdominal obesity's clinical relevance. These cost-effective indices could enhance early screening in resource-limited settings.
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Affiliation(s)
- Kaihao Wang
- Department of General Surgery, Xingtai People's Hospital, No.16 Hongxing Street, Xiangdu District, Xingtai, 054000, Hebei, China
| | - Anlei Wang
- Department of General Surgery, Xingtai People's Hospital, No.16 Hongxing Street, Xiangdu District, Xingtai, 054000, Hebei, China
| | - Shaozu Wang
- Department of General Surgery, Xingtai People's Hospital, No.16 Hongxing Street, Xiangdu District, Xingtai, 054000, Hebei, China
| | - Zhijiang Luo
- Department of General Surgery, Xingtai People's Hospital, No.16 Hongxing Street, Xiangdu District, Xingtai, 054000, Hebei, China
| | - Yazhao Gong
- Department of General Surgery, Xingtai People's Hospital, No.16 Hongxing Street, Xiangdu District, Xingtai, 054000, Hebei, China
| | - Xiaoliang Hao
- Department of General Surgery, Xingtai People's Hospital, No.16 Hongxing Street, Xiangdu District, Xingtai, 054000, Hebei, China
| | - Guanglei Yang
- Department of General Surgery, Xingtai People's Hospital, No.16 Hongxing Street, Xiangdu District, Xingtai, 054000, Hebei, China.
| | - Shuqing Xu
- Department of General Surgery, Xingtai People's Hospital, No.16 Hongxing Street, Xiangdu District, Xingtai, 054000, Hebei, China.
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15
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Gaston F, Polite B, Ullenius S, Fitzgerald S, Bajaj M. Sporadic Mucinous Adenocarcinoma of the Colon in an Adolescent Male: A Case Report and Review of the Literature. J Pediatr Hematol Oncol 2025:00043426-990000000-00564. [PMID: 40231812 DOI: 10.1097/mph.0000000000003031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Accepted: 02/14/2025] [Indexed: 04/16/2025]
Abstract
Colorectal cancer (CRC) is commonly seen in adult patients but makes up <1% of cancers in pediatric patients, with the largest known pediatric study having a sample size of 81 patients taken over a span of roughly 40 years. Patients typically present with nonspecific symptoms such as abdominal pain, nausea, and vomiting, which can result in the diagnosis being missed. Histopathology is typically unfavorable with signet ring colon cancer and mucinous adenocarcinoma with signet ring cell features being common. Treatment guidelines are based largely on adult protocols and include surgical resection followed by chemotherapy, with the addition of bevacizumab or cetuximab in higher-risk populations. In our case, we present a 17-year-old male with abdominal pain and weight loss who was found to have metastatic sporadic mucinous adenocarcinoma with signet ring cell features. Oncotype next-generation sequencing was found to be microsatellite stable, human epithelial growth factor receptor 2 negative, Kristen rat sarcoma viral oncogene homolog/v-raf murine sarcoma viral oncogene homolog B1/neuroblastoma reticular activating system wild type, and low tumor mutation burden with 3.7 mutations per megabase. He was treated with FOLFIRINOX at 70% dosing without bevacizumab due to recurrent admissions for small bowel obstructions and surgeries. Unfortunately, his cancer did not respond, so he proceeded with palliative chemotherapy. He expired 12 months later. This case raises the need for research on the biology of CRC in pediatric patients, as it is different from adults. It also underlines the necessity of the development of guidelines on CRC treatment in pediatric patients by initiating pediatric clinical trials or lowering the age of adult trials to under 18 years of age.
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Affiliation(s)
| | | | | | | | - Madhuri Bajaj
- University of Illinois College of Medicine Peoria
- Illinois CancerCare, Peoria
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16
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Wehbe S, Thomas RJ, Bolwell J, Butler R, Burke CA, Liska D, Macaron C. A Score to Predict Advanced Colorectal Neoplasia in Adults Younger than Age 45. Dig Dis Sci 2025; 70:1511-1520. [PMID: 39946063 PMCID: PMC11972222 DOI: 10.1007/s10620-025-08861-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 01/09/2025] [Indexed: 04/06/2025]
Abstract
BACKGROUND Early-onset colorectal cancer (CRC) requires identifying adults at heightened risk of advanced colorectal neoplasia (AN) who may warrant colonoscopy initiation < age 45 years. AIMS We aim to develop and validate a model estimating the likelihood of AN in adults age < 45 years. METHODS We performed a cross-sectional analysis of adults' ages 18-44 years who underwent a colonoscopy between 2011 and 2021 at a tertiary center. Subjects with AN constituted the case group while those with a normal colonoscopy or non-advanced neoplasia (NAN) formed the control group. We used backward elimination multivariable logistic regression methods to construct a model based on significant associations (p < 0.05) between risk factors and the presence of AN in a randomly selected training set and confirmed the associations in a validation set. RESULTS AN was detected in 346 (3.7%) of the 9,446 participants included. The reduced logistic regression model based on the training set identified BMI (p = 0.0157), family history of CRC (first-degree relative < 60, p < 0.0001; other family history of CRC p = 0.0117), and tobacco use (current vs. never, p = 0.0015, former vs. never, p = 0.0009) as risk factors for AN. In the validation set, the model exhibited moderate discriminatory power (c-statistic 0.645). The prediction score estimated the likelihood of detecting AN in the complete dataset, from 1.8% for individuals scoring 1 to > 14% for individuals scoring ≥ 9. CONCLUSION We developed and internally validated a simple score using clinical factors which successfully predicts the likelihood of AN in adults < 45 years undergoing colonoscopy. Once externally validated, the proposed risk score may be useful for individualized CRC screening strategies.
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Affiliation(s)
- Sarah Wehbe
- Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Raj Jessica Thomas
- Department of Internal Medicine, Cleveland Clinic Akron General, Akron, OH, USA
| | - Jacquelyn Bolwell
- Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Robert Butler
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
| | - Carol A Burke
- Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
- Young Onset Colorectal Cancer Center, Digestive Disease and Surgery Institute, A30 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
- Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - David Liska
- Young Onset Colorectal Cancer Center, Digestive Disease and Surgery Institute, A30 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA
- Colorectal Surgery, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Carole Macaron
- Gastroenterology and Hepatology, Digestive Disease and Surgery Institute, Cleveland Clinic, Cleveland, OH, USA.
- Young Onset Colorectal Cancer Center, Digestive Disease and Surgery Institute, A30 Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
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17
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Stetson A, Saluja S, Cameron DB, Mansfield SA, Polites SF, Honeyman JN, Dahl JP, Austin MT, Aldrink JH, Christison-Lagay ER. Surgical management of rare tumors (Part 1). Pediatr Blood Cancer 2025; 72 Suppl 2:e31287. [PMID: 39185712 DOI: 10.1002/pbc.31287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 08/07/2024] [Accepted: 08/10/2024] [Indexed: 08/27/2024]
Abstract
With an annual cumulative occurrence of approximately 15,000 in North America, all childhood cancers are rare. Very rare cancers as defined by both the European Cooperative Study Group for Rare Pediatric Cancers and the Children's Oncology Group fall into two principal categories: those so uncommon (fewer than 2 cases/million) that their study is challenging even through cooperative group efforts (e.g., pleuropulmonary blastoma and desmoplastic small round cell tumor) and those that are far more common in adults and therefore rarely studied in children (e.g., thyroid, melanoma, and gastrointestinal stromal tumor). Treatment strategies for these latter tumors are typically based on adult guidelines, although the pediatric variants of these tumors may harbor different genetic signatures and demonstrate different behavior. If melanoma and differentiated thyroid cancer are excluded, other rare cancer types account for only 2% of the cancers in children aged 0 to 14. This article highlights several of the most common rare tumor types.
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Affiliation(s)
- Alyssa Stetson
- Department of Surgery, Division of Pediatric Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Saurabh Saluja
- Division of General and Thoracic Surgery, The Hospital for Sick Children, Toronto, Ontario, Canada
| | - Danielle B Cameron
- Department of Surgery, Division of Pediatric Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Sara A Mansfield
- Division of General Pediatric Surgery, Nationwide Children's Hospital, Columbus, Ohio, USA
| | | | - Joshua N Honeyman
- Division of Pediatric Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA
| | - John P Dahl
- Division of Otolaryngology, Division of Pediatric Otolaryngology, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA
| | - Mary T Austin
- Department of Pediatric Surgery, University of Texas Health Science Center at Houston and Department of Surgical Oncology and Pediatrics, UT MD Anderson Cancer Center, Houston, Texas, USA
| | - Jennifer H Aldrink
- Division of General Pediatric Surgery, Nationwide Children's Hospital, Columbus, Ohio, USA
| | - Emily R Christison-Lagay
- Division of Pediatric Surgery, Yale School of Medicine, Yale-New Haven Hospital, New Haven, Connecticut, USA
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18
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Moazzam Z, Hawkins AT, Regenbogen SE, Holder-Murray J, Silviera M, Ejaz A, Balch GC, Khan A. Association of Enhanced Recovery After Surgery (ERAS) with textbook outcomes among patients undergoing surgery for rectal cancer. Surgery 2025; 180:109062. [PMID: 39793415 DOI: 10.1016/j.surg.2024.109062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 11/18/2024] [Accepted: 12/10/2024] [Indexed: 01/13/2025]
Abstract
BACKGROUND Surgical resection is the cornerstone of rectal cancer treatment but can be associated with adverse short-term postoperative outcomes. We sought to assess the factors associated with achievement of optimal outcomes among patients undergoing surgery for rectal cancer. METHODS In this multicenter retrospective cohort study, the US Rectal Cancer Consortium database was used to identify patients who underwent surgery for nonmetastatic rectal cancer between 2007 and 2018. The primary outcome was achievement of a Textbook Outcome. A Textbook Outcome is a composite outcome defined as the absence of any postoperative complications, extended length of stay (>75th percentile), 90-day readmission, and 90-day mortality. Multivariable logistic regression analyses were conducted to identify factors associated with the achievement of a Textbook Outcome, and reported as odds ratios and 95% confidence intervals. RESULTS Among 1,102 patients who underwent surgery for rectal cancer, Textbook Outcome was achieved by 41.8% (n = 461) of patients. On multivariable analyses, American Society of Anesthesiologists-Physical Status >2 (odds ratio 0.66, 95% confidence interval 0.50-0.88), diabetes (0.57, 0.38-0.87), operative time >3.5 hours (0.52, 0.39-0.69), and perioperative packed red blood cells transfusion (0.20, 0.12-0.34) were associated with decreased odds of achieving a Textbook Outcome. Conversely, Enhanced Recovery After Surgery was associated with increased odds of achieving a Textbook Outcome (1.93, 1.45-2.58). CONCLUSIONS AND RELEVANCE Despite improvement in recent years, short-term outcomes after rectal cancer surgery remain suboptimal. Patient optimization strategies such as Enhanced Recovery After Surgery are essential to facilitate the achievement of optimal outcomes in patients undergoing rectal cancer surgery.
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Affiliation(s)
- Zorays Moazzam
- Division of Colon and Rectal Surgery, Department of Surgery, Henry Ford Hospital, Detroit, MI.
| | - Alexander T Hawkins
- Division of Colon and Rectal Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN. https://twitter.com/alexhawkinsmd
| | - Scott E Regenbogen
- Division of Colon and Rectal Surgery, Department of Surgery, University of Michigan, Ann Arbor, MI. https://twitter.com/scottregenbogen
| | - Jennifer Holder-Murray
- Division of Colon and Rectal Surgery, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA. https://twitter.com/HolderMurray
| | - Matthew Silviera
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO
| | - Aslam Ejaz
- Division of Colon and Rectal Surgery, Department of Surgery, Emory University, Atlanta, GA. https://twitter.com/AEjaz85
| | - Glen C Balch
- Section of Colon and Rectal Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO
| | - Aimal Khan
- Division of Colon and Rectal Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, TN. https://twitter.com/AimalKhanMD
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19
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Shen Q, Zhou Y, Liu X, Li J, Pan S, Xie N, Lin X, Zhou L, Zhou J, Li T. Clinical and Genetic Characteristics of Pediatric Colorectal Cancer. Pediatr Blood Cancer 2025; 72:e31569. [PMID: 39887884 DOI: 10.1002/pbc.31569] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2024] [Revised: 12/21/2024] [Accepted: 01/18/2025] [Indexed: 02/01/2025]
Abstract
BACKGROUND Compared to colorectal cancer (CRC) in adults, CRC in children is extremely rare. Although its incidence has increased recently, there is a lack of clinical research on the disease. Inherited cancer susceptibility syndromes (ICSS), a group of disorders in which patients are predisposed to susceptibility to a wide range of tumors as a result of pathogenic mutations in genes in their germ line, are an important cause of CRC in children. Delayed diagnosis due to atypical clinical presentation, as well as limited awareness of ICSS among doctors, contributes to poor outcomes in juvenile CRC patients. Therefore, improving clinicians' understanding of the diagnosis and treatment of the disease is crucial to enhancing children's prognosis with CRC. METHODS Clinical data and laboratory reports were collected from eight pediatric patients diagnosed with CRC at the Children's Hospital of Nanjing Medical University between 2020 and 2023. The clinical and genetic characteristics of these patients were evaluated and compared with other patients with early-onset CRC in the literature. RESULTS A total of 8 children with CRC were enrolled in the study, including 5 male and 3 female children, with a median age of 140 (73-177) months. The main clinical manifestations were unexplained abdominal pain, abdominal distension, vomiting, and hematochezia. Three cases of intestinal obstruction and two cases of intestinal intussusception occurred among the patients. All eight children underwent surgical treatment, including one case of snare resection of rectal polyp, five cases of subtotal colectomy, and two cases of radical resection of CRC. One case of radical resection of CRC utilized laparoscopic and colonoscopic combined resection guided by indocyanine green (ICG) fluorescence navigation system. Postoperative combination of pathological pictures and immunohistochemical (IHC) staining results confirmed high-grade squamous intraepithelial lesion (HSIL) in Case 1, and mucinous adenocarcinoma in the remaining seven cases. Out of eight pediatric patients with CRC, except for Case 1 and Case 7, who did not undergo chemotherapy, the remaining six patients all received postoperative chemotherapy; among them, the patients in Cases 1, 6, 7, and 8 achieved complete remission, whereas the patients in Cases 2 and 4 died due to postoperative recurrence and distant metastasis, the patient in Case 3 is still undergoing chemotherapy, and the patient in Case 5 was lost to follow-up after surgery. The results of the genetic test report showed that two children had ICSS caused by mismatch gene repair system defects (deficient MMR, dMMR); in Case 3, the child's genetic test results showed heterozygous mutation of MSH2 in the MMR gene, with high microsatellite instability (MSI-H), and the results of the methylation test of the MLH1 gene were negative, which, combined with the family history of heterozygous mutation of the MSH2 gene, ruled out sporadic CRC and led to the diagnosis of Lynch syndrome (LS); Case 8 genetic testing showed two heterozygous mutations in the MMR gene PMS2 with microsatellite stabilization (MSS), and a diagnosis of constitutional mismatch repair deficiency (CMMRD) was considered. CONCLUSION Pediatric CRC is confronted with delayed diagnosis and poor clinical prognosis, mainly due to nonspecific clinical presentation and the low index of suspicion among clinicians. Early detection and diagnosis is the fundamental guarantee to improve the prognosis of pediatric CRC patients, and pediatric surgeons enhance the understanding of pediatric CRC and standardize the surgery as much as possible.
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Affiliation(s)
- Qiyang Shen
- Department of Oncology, Children's Hospital of Nanjing Medical University, Jiangsu, China
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Jiangsu, China
| | - Yong Zhou
- Department of Pediatric Surgery, Children's Hospital of Nanjing Medical University, Jiangsu, China
| | - Xingyu Liu
- Department of Pediatric Surgery, First Affiliated Hospital of Bengbu Medical College, Anhui, China
| | - Jian Li
- Department of Oncology, Children's Hospital of Nanjing Medical University, Jiangsu, China
| | - Sirui Pan
- Department of Oncology, Children's Hospital of Nanjing Medical University, Jiangsu, China
| | - Nan Xie
- Department of Oncology, Children's Hospital of Nanjing Medical University, Jiangsu, China
| | - Xinrong Lin
- Department of Oncology, Children's Hospital of Nanjing Medical University, Jiangsu, China
| | - Li Zhou
- Department of Oncology, Children's Hospital of Nanjing Medical University, Jiangsu, China
| | - Jianfeng Zhou
- Department of Oncology, Children's Hospital of Nanjing Medical University, Jiangsu, China
| | - Tao Li
- Department of Oncology, Children's Hospital of Nanjing Medical University, Jiangsu, China
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20
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Li Y, Piao Z, Ge X, Feng J, Sun D, Zhang J. Environmental pollutants and rectal cancer: The impact of water contamination. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 294:118072. [PMID: 40127547 DOI: 10.1016/j.ecoenv.2025.118072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 03/14/2025] [Accepted: 03/14/2025] [Indexed: 03/26/2025]
Abstract
BACKGROUND Water is a fundamental resource for life, and exposure to water contamination has far-reaching implications for an increased risk of tumor diseases. METHODS Studies of rectal and colorectal cancer related to water contamination were identified from the published literature in the PUBMED databases from 2010 to 2024. RESULTS This review provides a critical analysis of the current evidence, summarizing the association of water contamination, including industrial waste, pesticides, heavy metals, with rectal and colorectal cancer. It highlights their impact on rectal and colorectal cancer progression by underlying processes of DNA damage, chronic inflammation, and microbial contamination. CONCLUSION Rectal cancer is a significant global health concern with a strong association between environmental pollutants in water sources and increased incidence of rectal cancer. It is vital to identify how waster pollutants influence the development and progression of rectal cancer and formulate targeted preventive approaches and social interventions to decrease the disease's impact.
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Affiliation(s)
- Yezhou Li
- Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Zhe Piao
- Department of Neurology, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Xinbin Ge
- Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Jinbao Feng
- Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China
| | - Denghua Sun
- Department of Breast Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
| | - Jiayu Zhang
- Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, China.
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21
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Tang Z, Zhou G, Xu Y, Zhang Y. Survival analysis and prediction of early-onset colorectal cancer patients post-chemotherapy: an analysis based on the SEER database. Int J Colorectal Dis 2025; 40:74. [PMID: 40118983 PMCID: PMC11928432 DOI: 10.1007/s00384-025-04853-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/05/2025] [Indexed: 03/24/2025]
Abstract
BACKGROUND The incidence of Early-Onset Colorectal Cancer (EOCRC) has risen markedly in recent years, garnering widespread attention due to its distinctive clinical and biological features. However, systematic research on prognostic risk factors and long-term survival prediction for EOCRC patients undergoing postoperative chemotherapy remains scarce. This study seeks to pinpoint critical prognostic factors for EOCRC patients receiving postoperative chemotherapy and to devise a survival prediction tool employing a Nomogram model. METHODS Patients diagnosed with EOCRC between 2010 and 2015, who underwent postoperative chemotherapy, were extracted from the SEER (Surveillance, Epidemiology, and End Results) database. Only those meeting the inclusion criteria were included. Univariate and multivariate Cox regression analyses were performed to determine independent risk factors influencing overall survival (OS). A Nomogram model was then developed using significant variables. The model's predictive accuracy and clinical utility were assessed through the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). RESULTS A cohort of 9,205 patients was analyzed, with 6,445 randomly allocated to the training group and 2,760 to the validation group from the SEER database. Independent prognostic factors, including gender, race, marital status, primary tumor location, histological type, TNM stage, CEA levels, bone metastasis, liver metastasis, and lung metastasis, were identified through univariate and multivariate Cox regression analyses. A Nomogram model constructed from these factors yielded a C-index of 0.76 (0.75, 0.77) in the training group and 0.76 (0.75, 0.78) in the validation group, reflecting robust discriminative ability and consistency. The area under the curve (AUC) for predicting 1-year OS was calculated as 0.84 (0.81, 0.86) in the training group and 0.82 (0.78, 0.85) in the validation group. For 3-year OS, AUCs were recorded at 0.83 (0.82, 0.84) and 0.82 (0.80, 0.84), respectively, while for 5-year OS, AUCs reached 0.81 (0.80, 0.82) and 0.82 (0.80, 0.84). Calibration curves demonstrated close alignment between predicted and observed survival rates. Additionally, DCA affirmed the model's clinical decision-making value. CONCLUSION Prognostic risk factors for EOCRC patients receiving postoperative chemotherapy were systematically evaluated in this study, leading to the development of a Nomogram-based survival prediction model. This tool offers a robust scientific foundation for tailoring individualized treatment and guiding follow-up strategies.
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Affiliation(s)
- Zhiguo Tang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China
| | - Guojia Zhou
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China
| | - Yu Xu
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China
| | - Yinxu Zhang
- Department of General Surgery, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, China.
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22
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Kozak Y, Finiuk N, Czarnomysy R, Gornowicz A, Pinyazhko R, Lozynskyi A, Holota S, Klyuchivska O, Karkhut A, Polovkovych S, Klishch M, Stoika R, Lesyk R, Bielawski K, Bielawska A. Juglone-Bearing Thiopyrano[2,3-d]thiazoles Induce Apoptosis in Colorectal Adenocarcinoma Cells. Cells 2025; 14:465. [PMID: 40136714 PMCID: PMC11941218 DOI: 10.3390/cells14060465] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2025] [Revised: 03/14/2025] [Accepted: 03/18/2025] [Indexed: 03/27/2025] Open
Abstract
Colorectal cancer is a major global health challenge, with current treatments limited by toxicity and resistance. Thiazole derivatives, known for their bioactivity, are emerging as promising alternatives. Juglone (5-hydroxy-1,4-naphthoquinone) is a naturally occurring compound with known anticancer properties, and its incorporation into thiopyrano[2,3-d]thiazole scaffolds may enhance their therapeutic potential. This study examined the cytotoxicity of thiopyrano[2,3-d]thiazoles and their effects on apoptosis in colorectal cancer cells. Les-6547 and Les-6557 increased the population of ROS-positive HT-29 cancer cells approximately 10-fold compared with control cells (36.3% and 38.5% vs. 3.8%, respectively), potentially contributing to various downstream effects. Elevated ROS levels were associated with cell cycle arrest, inhibition of DNA biosynthesis, and reduced cell proliferation. A significant shift in the cell cycle distribution was observed, with an increase in S-phase (from 17.3% in the control to 34.7% to 51.3% for Les-6547 and Les-6557, respectively) and G2/M phase (from 24.3% to 39.9% and 28.8%). Additionally, Les-6547 and Les-6557 inhibited DNA biosynthesis in HT-29 cells, with IC50 values of 2.21 µM and 2.91 µM, respectively. Additionally, ROS generation may initiate the intrinsic apoptotic pathway. Les-6547 and Les-6557 activated both intrinsic and extrinsic apoptotic pathways, demonstrated by notable increases in the activity of caspase 3/7, 8, 9, and 10. This study provides a robust basis for investigating the detailed molecular mechanisms of action and therapeutic potential of Les-6547 and Les-6557.
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Affiliation(s)
- Yuliia Kozak
- Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology of National Academy of Sciences of Ukraine, Drahomanov 14/16, 79005 Lviv, Ukraine; (N.F.); (O.K.); (M.K.); (R.S.)
| | - Nataliya Finiuk
- Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology of National Academy of Sciences of Ukraine, Drahomanov 14/16, 79005 Lviv, Ukraine; (N.F.); (O.K.); (M.K.); (R.S.)
| | - Robert Czarnomysy
- Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1, 15-089 Białystok, Poland; (R.C.); (K.B.)
| | - Agnieszka Gornowicz
- Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1, 15-089 Białystok, Poland;
| | - Roman Pinyazhko
- Department of Normal Physiology, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine;
| | - Andrii Lozynskyi
- Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine; (A.L.); (S.H.); (R.L.)
| | - Serhii Holota
- Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine; (A.L.); (S.H.); (R.L.)
| | - Olga Klyuchivska
- Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology of National Academy of Sciences of Ukraine, Drahomanov 14/16, 79005 Lviv, Ukraine; (N.F.); (O.K.); (M.K.); (R.S.)
| | - Andriy Karkhut
- Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytecnic National University, Bandera 12, 79013 Lviv, Ukraine; (A.K.); (S.P.)
| | - Svyatoslav Polovkovych
- Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytecnic National University, Bandera 12, 79013 Lviv, Ukraine; (A.K.); (S.P.)
| | - Mykola Klishch
- Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology of National Academy of Sciences of Ukraine, Drahomanov 14/16, 79005 Lviv, Ukraine; (N.F.); (O.K.); (M.K.); (R.S.)
| | - Rostyslav Stoika
- Department of Regulation of Cell Proliferation and Apoptosis, Institute of Cell Biology of National Academy of Sciences of Ukraine, Drahomanov 14/16, 79005 Lviv, Ukraine; (N.F.); (O.K.); (M.K.); (R.S.)
| | - Roman Lesyk
- Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine; (A.L.); (S.H.); (R.L.)
- Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszów, Sucharskiego 2, 35-225 Rzeszów, Poland
| | - Krzysztof Bielawski
- Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1, 15-089 Białystok, Poland; (R.C.); (K.B.)
| | - Anna Bielawska
- Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, Kilinskiego 1, 15-089 Białystok, Poland;
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23
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Varde A, McVeigh T, Cuthill V, Brady AF, DeSouza B, Latchford A, Monahan KJ. Addressing uncertainty in hereditary colorectal cancer: the role of a regional expert multidisciplinary team meeting. Fam Cancer 2025; 24:26. [PMID: 40045045 PMCID: PMC11882607 DOI: 10.1007/s10689-025-00451-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 02/23/2025] [Indexed: 03/09/2025]
Abstract
There is frequent uncertainty in both the precise quantification of risk, and the application of clinical interventions, designed to mitigate increased heritable colorectal cancer (CRC) susceptibility. We evaluated the role of a collaborative specialist multidisciplinary team meeting (MDM) for familial and hereditary CRC, led by the St Mark's Hospital Centre for Familial Intestinal Cancer specifically in supporting the clinical management of uncertainty. A retrospective thematic analysis of meeting outcomes from inception in June 2020 until March 2023 was performed. Descriptive statistics were employed to ascertain clinicopathological data, clinical queries and whether MDM recommendations were outside the scope of current guidelines. In total 260 cases were discussed from 13 regional institutions. A prior personal history of cancer was present in 215 (82.6%), and a family history of CRC in 107(41.2%) and non-CRC 27(10.4%) cases. In thematic analysis uncertainty related to indications for genetic testing was considered in 148 (56.9%) of cases, with unexplained mismatch repair deficiency (u-dMMR) in 78 (30%) of cases, and resolution of molecular interpretation in 61 (23.5%). Surveillance related queries represented 55 (21.1%), and mainstreaming 29 (11%) of cases. Management was recommended beyond the scope of existing guidelines in 64 (24.6%) cases. This regional hereditary CRC MDM provides clinicians with support in areas of uncertainty in diagnosis and clinical management, supporting clinical decision-making where evidence and clinical guidelines may be limited. This model could be replicated to support complexity in clinical care in other geographical regions or other health conditions.
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Affiliation(s)
- Avani Varde
- The Centre for Familial Intestinal Cancer, St Mark's The National Bowel Hospital, Acton Lane, Park Royal, London, NW10 7NS, UK
- Surgery and Cancer, Imperial College, London, UK
| | | | - Vicky Cuthill
- The Centre for Familial Intestinal Cancer, St Mark's The National Bowel Hospital, Acton Lane, Park Royal, London, NW10 7NS, UK
| | - Angela F Brady
- North West Thames Regional Genetics Service, London, UK
- Surgery and Cancer, Imperial College, London, UK
| | - Bianca DeSouza
- North West Thames Regional Genetics Service, London, UK
- Surgery and Cancer, Imperial College, London, UK
| | - Andrew Latchford
- The Centre for Familial Intestinal Cancer, St Mark's The National Bowel Hospital, Acton Lane, Park Royal, London, NW10 7NS, UK
- Surgery and Cancer, Imperial College, London, UK
| | - Kevin J Monahan
- The Centre for Familial Intestinal Cancer, St Mark's The National Bowel Hospital, Acton Lane, Park Royal, London, NW10 7NS, UK.
- Surgery and Cancer, Imperial College, London, UK.
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24
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Buhaya MH, Huang EH. Deciphering Early-Onset Colorectal Cancer: Molecular Profiling of the Tumor Microenvironment. Dis Colon Rectum 2025; 68:257-260. [PMID: 39625394 DOI: 10.1097/dcr.0000000000003447] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/22/2025]
Affiliation(s)
- Munir H Buhaya
- Department of Surgery, University of Texas Southwestern, Dallas, Texas
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25
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Ayer D, Jain A, Singh M, Tawfik A, Tadros M. Understanding TikTok's Role in Young-Onset Colorectal Cancer Awareness and Education. JOURNAL OF CANCER EDUCATION : THE OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER EDUCATION 2025:10.1007/s13187-025-02585-3. [PMID: 39992546 DOI: 10.1007/s13187-025-02585-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/08/2025] [Indexed: 02/25/2025]
Abstract
The incidence of colorectal cancer (CRC) in younger adults has risen by about 1-2% annually in the past decade. TikTok has become a popular venue for the discussion of health information among young adults. This study analyzed the top 85 most-liked TikToks under the search terms "early colon cancer" and "young adult colon cancer," to evaluate their educational value. Data on the post uploader, content, analytics, and mentioned tips/symptoms were collected. Two independent researchers rated the quality of each video using a global quality score (GQS). The videos analyzed had a total of over 37 million views. Among them, 16.47% highlighted how misinformation contributed to delayed diagnoses, yet only 2.35% specifically educated viewers about such misinformation. Provider-posted content had higher GQS ratings than non-provider content (p < 0.05), indicating better quality, although total views were higher for non-provider content. The GQS did not differ significantly between highly viewed (> 100,000 views) and lower-viewed (≤ 100,000 views) videos. Our results highlight that TikTok is a key platform for engaging young adults about rising CRC rates, though increased expert engagement is needed to address current gaps in combating misinformation and promoting high-quality educational content.
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Affiliation(s)
| | | | | | | | - Micheal Tadros
- Division of Gastroenterology, Albany Medical Center, Albany, NY, USA.
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26
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Ionescu VA, Gheorghe G, Baban IA, Barbu A, Georgescu TF, Tiuca LC, Iacobus NA, Diaconu CC. Prognostic Differences Between Early-Onset and Late-Onset Colorectal Cancer. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:390. [PMID: 40142201 PMCID: PMC11944167 DOI: 10.3390/medicina61030390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Revised: 02/18/2025] [Accepted: 02/23/2025] [Indexed: 03/28/2025]
Abstract
Background and Objectives: Early-onset colorectal cancer (EO-CRC) has become a significant public health concern due to its alarming rise in incidence and the poor prognosis associated with this disease. The aim of our study was to identify epidemiological, clinical, and paraclinical characteristics that could explain the more aggressive evolution of EO-CRC compared to late-onset colorectal cancer (LO-CRC). Materials and Methods: We conducted a retrospective study over a two-year period, including 204 patients diagnosed with colorectal cancer (CRC). The patients were divided into two subgroups: those with EO-CRC and those with LO-CRC. Statistical analysis was performed using IBM SPSS Statistics, Version 29.0. Results: EO-CRC was identified in 11.3% of the patients included in the study. Compared to LO-CRC patients, EO-CRC patients exhibited a tendency for more distal tumor localization and a stenotic endoscopic appearance (43.5% vs. 29.3%). Regarding histopathological diagnosis, EO-CRC patients demonstrated a higher proportion of the mucinous histologic subtype (34.8% vs. 14.4%) and a significantly greater percentage of poorly differentiated tumors (39.1% vs. 14.5%; p = 0.010). Immunohistochemical results, available for a limited number of patients, revealed higher CDX2 positivity in LO-CRC patients (p = 0.012) and higher HER2 positivity in EO-CRC patients (p = 0.002). Smoking (p = 0.006) and hypertension (p = 0.002) were more prevalent in EO-CRC patients than in LO-CRC patients. Conclusions: Patients with EO-CRC exhibit distinct histopathological and molecular characteristics compared to those with LO-CRC, which may contribute to their poorer prognoses. The higher prevalence of the mucinous histological subtype, poor tumor differentiation, increased HER2 expression, and reduced CDX2 expression suggest potential molecular pathways driving the aggressive nature of EO-CRC. These findings highlight the need for tailored screening strategies and personalized therapeutic approaches in younger CRC patients. Future studies should further investigate the underlying mechanisms and potential biomarkers that could guide early diagnoses and targeted treatments.
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Affiliation(s)
- Vlad Alexandru Ionescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (T.F.G.); (L.-C.T.); (N.A.I.); (C.C.D.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Gina Gheorghe
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (T.F.G.); (L.-C.T.); (N.A.I.); (C.C.D.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Ioana-Alexandra Baban
- Gastroenterology Department, Central Military Emergency University Hospital, 010825 Bucharest, Romania; (I.-A.B.); (A.B.)
| | - Alexandru Barbu
- Gastroenterology Department, Central Military Emergency University Hospital, 010825 Bucharest, Romania; (I.-A.B.); (A.B.)
| | - Teodor Florin Georgescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (T.F.G.); (L.-C.T.); (N.A.I.); (C.C.D.)
- General Surgery Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Loredana-Crista Tiuca
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (T.F.G.); (L.-C.T.); (N.A.I.); (C.C.D.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Ninel Antonie Iacobus
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (T.F.G.); (L.-C.T.); (N.A.I.); (C.C.D.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
| | - Camelia Cristina Diaconu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila Bucharest, 050474 Bucharest, Romania; (G.G.); (T.F.G.); (L.-C.T.); (N.A.I.); (C.C.D.)
- Internal Medicine Department, Clinical Emergency Hospital of Bucharest, 105402 Bucharest, Romania
- Academy of Romanian Scientists, 050085 Bucharest, Romania
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Feng R, Li X, Li B, Luan T, He J, Liu G, Yue J. Integrating transcriptomics and scPagwas analysis predicts naïve CD4 T cell-related gene DRAM2 as a potential biomarker and therapeutic target for colorectal cancer. BMC Cancer 2025; 25:317. [PMID: 39984869 PMCID: PMC11843817 DOI: 10.1186/s12885-025-13731-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 02/13/2025] [Indexed: 02/23/2025] Open
Abstract
OBJECTIVE The interaction between T cells, particularly naïve CD4 T cells (CD4Tn), and colorectal cancer (CRC) is highly complex. CD4Tn play a crucial role in modulating immune responses within the tumor microenvironment, yet the precise mechanisms by which they influence tumor progression remain elusive. This study aims to explore the relationship between CRC and CD4Tn, identify biomarkers and therapeutic targets, and focus on the role of CD4Tn in shaping the immune environment of CRC. METHODS Single-cell transcriptomics, alongside the scPagwas algorithm, were employed to identify pivotal T cell subsets involved in CRC progression. Bulk transcriptomic data were further analyzed using deconvolution algorithms to elucidate the roles of these key T cell subsets. The abundance of naïve CD4 T cells (CD4Tn) was specifically assessed to gauge patient responses to immunotherapy, alterations in the immune microenvironment, and correlations with genetic mutations. Key genes linked to CD4Tn were identified using weighted gene co-expression network analysis and Pearson correlation scores. The SMR algorithm was subsequently used for validation, with experimental verification following. RESULTS Through single-cell transcriptomics and the scPagwas algorithm, CD4Tn was confirmed as a critical cell type in CRC progression. High infiltration of CD4Tn cells in CRC patients was correlated with poorer prognosis and suboptimal responses to immunotherapy. SMR analysis suggested a potential causal link between DRAM2 gene expression and CRC progression. Experimental knockdown of DRAM2 in colorectal cancer cells significantly inhibited tumor growth. CONCLUSION The DRAM2 gene, associated with CD4Tn cells, appears to play a pivotal role in the advancement of CRC and may represent a promising therapeutic target for treatment.
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Affiliation(s)
- Rui Feng
- Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiaofang Li
- Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Benhua Li
- The Second People's Hospital of Liangshan Yi Autonomous Prefecture, Xichang, China
| | - Tiankuo Luan
- Department of Human Anatomy, Basic Medical School, Chongqing Medical University, Chongqing, China
| | - Jiaming He
- Department of Human Anatomy, Basic Medical School, Chongqing Medical University, Chongqing, China
| | - Guojing Liu
- Department of Neurosurgery, The University-Town Hospital of Chongqing Medical University, NO.55 of university-town middle Road, Shapingba District, Chongqing, 400000, China.
| | - Jian Yue
- Department of Breast Surgery, Gaozhou People's Hospital, No.89 Xiguan Road, Gaozhou, Guangdong, 525200, China.
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Luo LZ, Kim JH, Herrera I, Wu S, Wu X, Park SS, Cho J, Cope L, Xian L, West BE, Calderon-Espinosa J, Kim J, Thompson Z, Maloo I, Larman T, Reddy KL, Feng Y, Fearon ER, Sears CL, Resar L. HMGA1 acts as an epigenetic gatekeeper of ASCL2 and Wnt signaling during colon tumorigenesis. J Clin Invest 2025; 135:e184442. [PMID: 39895630 PMCID: PMC11785931 DOI: 10.1172/jci184442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 11/27/2024] [Indexed: 02/04/2025] Open
Abstract
Mutated tumor cells undergo changes in chromatin accessibility and gene expression, resulting in aberrant proliferation and differentiation, although how this occurs is unclear. HMGA1 chromatin regulators are abundant in stem cells and oncogenic in diverse tissues; however, their role in colon tumorigenesis is only beginning to emerge. Here, we uncover a previously unknown epigenetic program whereby HMGA1 amplifies Wnt signaling during colon tumorigenesis driven by inflammatory microbiota and/or Adenomatous polyposis coli (Apc) inactivation. Mechanistically, HMGA1 "opens" chromatin to upregulate the stem cell regulator, Ascl2, and downstream Wnt effectors, promoting stem and Paneth-like cell states while depleting differentiated enterocytes. Loss of just one Hmga1 allele within colon epithelium restrains tumorigenesis and Wnt signaling driven by mutant Apc and inflammatory microbiota. However, HMGA1 deficiency has minimal effects in colon epithelium under homeostatic conditions. In human colon cancer cells, HMGA1 directly induces ASCL2 by recruiting activating histone marks. Silencing HMGA1 disrupts oncogenic properties, whereas reexpression of ASCL2 partially rescues these phenotypes. Further, HMGA1 and ASCL2 are coexpressed and upregulated in human colorectal cancer. Together, our results establish HMGA1 as an epigenetic gatekeeper of Wnt signals and cell state under conditions of APC inactivation, illuminating HMGA1 as a potential therapeutic target in colon cancer.
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Affiliation(s)
- Li Z. Luo
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Jung-Hyun Kim
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Research Institute, National Cancer Center, Goyang-si, Gyeonggido, Republic of Korea
| | - Iliana Herrera
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Shaoguang Wu
- Division of Infectious Diseases, Department of Medicine
| | - Xinqun Wu
- Division of Infectious Diseases, Department of Medicine
| | - Seong-Sik Park
- Research Institute, National Cancer Center, Goyang-si, Gyeonggido, Republic of Korea
| | - Juyoung Cho
- Research Institute, National Cancer Center, Goyang-si, Gyeonggido, Republic of Korea
| | - Leslie Cope
- Sidney Kimmel Comprehensive Cancer Center, Division of Biostatistics
| | - Lingling Xian
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Bailey E. West
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Pathobiology Graduate Program, Department of Pathology, and
| | - Julian Calderon-Espinosa
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Human Genetics Graduate Program, Department of Genetics and Molecular Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Joseph Kim
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Zanshé Thompson
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Isha Maloo
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Biochemistry and Molecular Biology Program, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | | | - Karen L. Reddy
- Department of Biological Chemistry, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ying Feng
- Department of Oncology, University of Michigan, Ann Arbor, Michigan, USA
| | - Eric R. Fearon
- Department of Oncology, University of Michigan, Ann Arbor, Michigan, USA
| | - Cynthia L. Sears
- Division of Infectious Diseases, Department of Medicine
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, and
- Molecular Immunology, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Linda Resar
- Division of Hematology, Department of Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Sidney Kimmel Comprehensive Cancer Center, Division of Biostatistics
- Pathobiology Graduate Program, Department of Pathology, and
- Human Genetics Graduate Program, Department of Genetics and Molecular Medicine, the Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Biochemistry and Molecular Biology Program, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
- Department of Pathology and
- Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, and
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Moiz S, Saha B, Mondal V, Bishnu D, Das B, Bose B, Das S, Banerjee N, Dutta A, Chatterjee K, Goswami S, Mukhopadhyay S, Basu S. Differential Expression of miRNAs Between Young-Onset and Late-Onset Indian Colorectal Carcinoma Patients. Noncoding RNA 2025; 11:10. [PMID: 39997610 PMCID: PMC11858122 DOI: 10.3390/ncrna11010010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 01/13/2025] [Accepted: 01/21/2025] [Indexed: 02/26/2025] Open
Abstract
Reports indicate a worldwide increase in the incidence of Early-Onset Colorectal Carcinoma (EOCRC) (<50 years old). In an effort to understand the different modes of pathogenesis in early-onset CRC, colorectal tumors from EOCRC (<50 years old) and Late-Onset patients (LOCRC; >50 years old) were screened to eliminate microsatellite instability (MSI), nuclear β-catenin, and APC mutations, as these are known canonical factors in CRC pathogenesis. Small-RNA sequencing followed by comparative analysis revealed differential expression of 23 miRNAs (microRNAs) specific to EOCRC and 11 miRNAs specific to LOCRC. We validated the top 10 EOCRC DEMs in TCGA-COAD and TCGA-READ cohorts, followed by validation in additional EOCRC and LOCRC cohorts. Our integrated analysis revealed upregulation of hsa-miR-1247-3p and hsa-miR-148a-3p and downregulation of hsa-miR-326 between the two subsets. Experimentally validated targets of the above miRNAs were compared with differentially expressed genes in the TCGA dataset to identify targets with physiological significance in EOCRC development. Our analysis revealed metabolic reprogramming, downregulation of anoikis-regulating pathways, and changes in tissue morphogenesis, potentially leading to anchorage-independent growth and progression of epithelial-mesenchymal transition (EMT). Upregulated targets include proteins present in the basal part of intestinal epithelial cells and genes whose expression is known to correlate with invasion and poor prognosis.
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Affiliation(s)
- Sumaiya Moiz
- Department of Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata 700094, India; (S.M.); (V.M.); (D.B.)
| | - Barsha Saha
- Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani 741251, India; (B.S.); (S.G.)
- Regional Centre for Biotechnology, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad 121001, India
| | - Varsha Mondal
- Department of Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata 700094, India; (S.M.); (V.M.); (D.B.)
- Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, NY 12208, USA
| | - Debarati Bishnu
- Department of Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata 700094, India; (S.M.); (V.M.); (D.B.)
| | - Biswajit Das
- Department of Histopathology, Netaji Subhas Chandra Bose Cancer Hospital, Kolkata 700094, India; (B.D.); (N.B.); (A.D.); (K.C.)
| | - Bodhisattva Bose
- Department of Surgical Oncology, All India Institute of Medical Sciences (AIIMS), Rishikesh 249203, India;
- Department of General Surgery, Nil Ratan Sircar Medical College and Hospital, Kolkata 700014, India
| | - Soumen Das
- Department of Surgical Oncology, Netaji Subhas Chandra Bose Cancer Hospital, Kolkata 700094, India;
| | - Nirmalya Banerjee
- Department of Histopathology, Netaji Subhas Chandra Bose Cancer Hospital, Kolkata 700094, India; (B.D.); (N.B.); (A.D.); (K.C.)
- Department of Histopathology, Narayana Superspeciality Hospital, Kolkata 700099, India
| | - Amitava Dutta
- Department of Histopathology, Netaji Subhas Chandra Bose Cancer Hospital, Kolkata 700094, India; (B.D.); (N.B.); (A.D.); (K.C.)
| | - Krishti Chatterjee
- Department of Histopathology, Netaji Subhas Chandra Bose Cancer Hospital, Kolkata 700094, India; (B.D.); (N.B.); (A.D.); (K.C.)
- Department of Pathology, Neotia Bhagirathi Woman and Child Care Centre, Kolkata 700017, India
| | - Srikanta Goswami
- Biotechnology Research and Innovation Council-National Institute of Biomedical Genomics (BRIC-NIBMG), Kalyani 741251, India; (B.S.); (S.G.)
- Regional Centre for Biotechnology, 3rd Milestone, Faridabad-Gurugram Expressway, Faridabad 121001, India
| | - Soma Mukhopadhyay
- Department of Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata 700094, India; (S.M.); (V.M.); (D.B.)
| | - Sudarshana Basu
- Department of Molecular Biology, Netaji Subhas Chandra Bose Cancer Research Institute, Kolkata 700094, India; (S.M.); (V.M.); (D.B.)
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Abdul Jalal MI, Mohd Azhar AT, Kamaruddin MA, Alias MR, Abd Jalal N, Ismail N, Chin SF, Goh YX, Abdullah N, Sagap I, Mohd Azman ZA, Aizuddin AN, Mohamed Nawi A, Ismail NH, Jamal R, Abdul Murad NA. Colorectal Cancer Screening using Immunochemical Faecal Occult Blood Testing (iFOBT) in Urban-Poor Communities in Cheras, Malaysia: A Cross-Sectional Study. Malays J Med Sci 2025; 32:154-168. [PMID: 40417191 PMCID: PMC12097158 DOI: 10.21315/mjms-09-2024-726] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Accepted: 12/30/2024] [Indexed: 05/27/2025] Open
Abstract
Background Colorectal cancer (CRC) is one of the most common cancers globally, with the immunochemical faecal occult blood test (iFOBT) frequently used for population level screening. This study evaluated CRC screening uptake among urban-poor individuals aged 40-65, assessed their knowledge of CRC risk factors and symptoms before and after an educational programme, and identified determinants of polyps and CRC within this group. Methods A cross-sectional study recruited 577 individuals from seven People's Residential Project (PPR) areas in Cheras, Kuala Lumpur and Malaysia Madani Carnival between March 2022 and July 2023. Inclusion criteria were age 40-65 and smartphone ownership, excluding those with CRC history, acute gastritis, inflammatory bowel disease, or recent CRC screening. The iFOBT was administered, followed by questionnaires and educational talks. A follow-up questionnaire was conducted via phone two weeks post-programme. Results Overall, 321 participants fulfilled the eligibility criteria. Most iFOBT-positive participants were in their 50s (median [interquartile range, IQR]: 56 [16]), female (65%), 86.3% non-smokers, and 62.5% with moderate CRC risk based on the Asia Pacific Colorectal Screening (APCS) Score, showing no significant differences from iFOBT-negative participants. Among the 267 who returned iFOBT kits, 30.0% tested positive, with 28.8% undergoing colonoscopy. Polyps and CRC were detected in 21.74% and 4.35% of the participants, respectively. The mean knowledge score on CRC symptoms was significantly lower post-programme, with no significant change in awareness of CRC risk factors. Conclusion Detection rates for polyps and CRC are low. Awareness of CRC symptoms is higher pre-screening than post-screening, highlighting challenges in conducting CRC education in urban-poor communities.
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Affiliation(s)
| | - Ahmad Termidzi Mohd Azhar
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Mohd Arman Kamaruddin
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Mohd Raziff Alias
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Nazihah Abd Jalal
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Norliza Ismail
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Siok-Fong Chin
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Ying-Xian Goh
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Noraidatulakma Abdullah
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Ismail Sagap
- Hospital Tunku Ampuan Besar Tuanku Aishah Rohani, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Zairul Azwan Mohd Azman
- Hospital Canselor Tuanku Muhriz, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Azimatun Noor Aizuddin
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Azmawati Mohamed Nawi
- Department of Public Health Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Nor Halizam Ismail
- Department of Health and Environment, Dewan Bandaraya Kuala Lumpur, Cheras, Kuala Lumpur, Malaysia
| | - Rahman Jamal
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
| | - Nor Azian Abdul Murad
- UKM Medical Molecular Biology Institute, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, Malaysia
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Alshenaifi JY, Vetere G, Maddalena G, Yousef M, White MG, Shen JP, Vilar E, Parseghian C, Dasari A, Morris VK, Huey R, Overman MJ, Wolff R, Raghav KP, Willis J, Alfaro K, Futreal A, You YN, Kopetz S. Mutational and co-mutational landscape of early onset colorectal cancer. Biomarkers 2025; 30:64-76. [PMID: 39761813 PMCID: PMC11856746 DOI: 10.1080/1354750x.2024.2447089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Accepted: 12/20/2024] [Indexed: 01/11/2025]
Abstract
INTRODUCTION Colorectal cancer (CRC) incidence and mortality before 50 have been rising alarmingly in the recent decades. METHODS Using a cohort of 10,000 patients, this study investigates the clinical, mutational, and co-mutational features of CRC in early-onset (EOCRC, < 50 years) compared to late-onset (LOCRC, ≥ 50 years). RESULTS EOCRC was associated with a higher prevalence of Asian and Hispanic patients, rectal or left-sided tumors (72% vs. 59%), and advanced-stage disease. Molecular analyses revealed differences in mutation patterns, with EOCRC having higher frequencies of TP53 (74% vs. 68%, p < 0.01) and SMAD4 (17% vs. 14%, p = 0.015), while BRAF (5% vs. 11%, p < 0.001) and NOTCH1 (2.7% vs. 4.1%, p = 0.01) mutations were more prevalent in LOCRC. Stratification by tumor site and MSI status highlighted significant location- and age-specific molecular differences, such as increased KRAS and CTNNB1 mutations in right-sided EOCRC and higher BRAF prevalence in MSI-H LOCRC (47% vs. 6.7%, p < 0.001). Additionally, co-occurrence analysis revealed unique mutational networks in EOCRC MSS, including significant co-occurrences of FBXW7 with NOTCH3, RB1, and PIK3R1. CONCLUSION This study highlights the significance of age-specific molecular profiling, offering insights into the unique biology of EOCRC and potential clinical applications.
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Affiliation(s)
- Jumanah Yousef Alshenaifi
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Guglielmo Vetere
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Giulia Maddalena
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Mahmoud Yousef
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Michael G. White
- Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - John Paul Shen
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Eduardo Vilar
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Christine Parseghian
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Arvind Dasari
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Van Karlyle Morris
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Ryan Huey
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Michael J. Overman
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Robert Wolff
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Kanwal P. Raghav
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Jason Willis
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Kristin Alfaro
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Andy Futreal
- Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Y. Nancy You
- Department of Colon & Rectal Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
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Zeng W, Sun Y, Liao Z, Xu J. A predictive nomogram for predicting liver metastasis in early-onset colon cancer: a population-based study. Transl Cancer Res 2025; 14:545-553. [PMID: 39974390 PMCID: PMC11833359 DOI: 10.21037/tcr-24-1159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 11/10/2024] [Indexed: 02/21/2025]
Abstract
Background The risk of liver metastasis (LM) may be estimated using predictive nomograms. While the nomogram has recently been applied in oncology, there are relatively few studies concentrating on predicting LM in patients with early-onset colon cancer. We aimed to identify independent risk factors for LM in patients with early-onset colon cancer and develop a nomogram for predicting the probability of LM in these patients. Methods Our study encompassed 4,890 early-onset colon cancer patients with LM who were registered in the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. These patients were randomly allocated into training and validation cohorts at a ratio of 7:3. Univariate and multivariate logistic regression analyses were conducted to identify the independent risk factors for LM, and a nomogram was developed using these factors. The model's discriminatory power, accuracy, and clinical utility were evaluated using receiver operating characteristics (ROC), calibration, and decision curve analyses. Results Overall, 4,890 patients with early-onset colon cancer and LM were selected from the SEER database. LM incidence in these patients was 18.4%. Univariate and multivariate analyses revealed histological type, T stage, N stage, and carcinoembryonic antigen (CEA) level as independent risk factors. ROC curve analysis revealed that the predictive nomogram for LM risk had an area under the curve of 0.812 [95% confidence interval (CI): 0.795-0.829] and 0.809 (95% CI: 0.784-0.834) in the training and validation sets, respectively, demonstrating good discriminatory ability of the model. Calibration curve analysis showed good agreement between predicted values from the nomogram and actual observations, and the decision curve analysis (DCA) demonstrated the high clinical utility of the nomogram. Conclusions LM incidence was higher in patients with early-onset colon cancer. Our nomogram demonstrates a high level of efficacy in predicting the risk of LM in patients with early-onset colon cancer, thereby assisting clinicians in making well-informed treatment decisions prior to further intervention.
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Affiliation(s)
- Weichao Zeng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- Department of Gastrointestinal Surgery, The Second Clinical School of Medicine, Fujian Medical University, Quanzhou, China
| | - Yafeng Sun
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- Department of Gastrointestinal Surgery, The Second Clinical School of Medicine, Fujian Medical University, Quanzhou, China
| | - Zhengrong Liao
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- Department of Gastrointestinal Surgery, The Second Clinical School of Medicine, Fujian Medical University, Quanzhou, China
| | - Jianhua Xu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
- Department of Gastrointestinal Surgery, The Second Clinical School of Medicine, Fujian Medical University, Quanzhou, China
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Wang G, Pan S. The impact of sleep interventions combined with enhanced nutritional support on sleep quality, nutritional status, pain management, psychological well-being, and quality of life in postoperative colon cancer patients. J Cancer Res Clin Oncol 2025; 151:50. [PMID: 39869202 PMCID: PMC11772530 DOI: 10.1007/s00432-025-06093-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2024] [Accepted: 01/13/2025] [Indexed: 01/28/2025]
Abstract
OBJECTIVE To investigate the synergistic effects of combined sleep interventions and enhanced nutritional support on postoperative recovery in colon cancer patients, with a focus on sleep quality, nutritional status, pain management, psychological well-being, and quality of life. METHODS This randomized controlled trial included 290 postoperative colon cancer patients admitted to the First Affiliated Hospital of Soochow University between May 2021 and May 2023. Participants were randomized into two groups: the intervention group, which received standard care supplemented with sleep and nutritional interventions, and the control group, which received standard care alone. Outcomes were assessed pre- and post-intervention, including the Pittsburgh Sleep Quality Index (PSQI), nutritional markers (serum albumin, prealbumin, body weight, etc.), Visual Analog Scale (VAS) for pain, Self-Rating Anxiety and Depression Scales (SAS, SDS), and EORTC QLQ-C30 quality of life scores. RESULTS The intervention group demonstrated significantly greater improvements across all assessed domains compared to the control group ( P < 0.005 after Bonferroni correction). Sleep quality (PSQI: 7.81 vs. 10.43, d = 0.81) and nutritional markers (e.g., prealbumin: 230.19 mg/L vs. 188.01 mg/L, d = 1.21 ) improved markedly. Similarly, reductions in pain (VAS: 2.65 vs. 5.19,d = 1.09 ), anxiety (SAS: 42.03 vs. 49.45, d = 0.88), and depression (SDS: 38.17 vs. 49.77,d = 1.02 ) were observed. Quality of life scores significantly increased in the intervention group compared to the control group (EORTC QLQ-C30: 99.29 vs. 88.41, d = 0.92). CONCLUSION The combined intervention of sleep enhancement and nutritional support significantly accelerated postoperative recovery in colon cancer patients, demonstrating synergistic effects that improved physical, psychological, and quality-of-life outcomes. These findings underscore the value of integrating multifaceted interventions into standard postoperative care to optimize recovery trajectories and overall well-being.
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Affiliation(s)
- Gang Wang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou City, Jiangsu Province, China
| | - Shengjie Pan
- Department of Neurology, The First Affiliated Hospital of Soochow University, 899 Pinghai Road, Suzhou City, Jiangsu Province, China.
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Pezzoli A, Buttitta F, Palmonari C, Simoni M, Pierantoni C, Merighi A, Ricciardiello L. Prevalence and Endoscopic Features of Colorectal Non-Polypoid Lesions: A Single-Center Retrospective Study from a Large Cohort of Fecal Immunochemical Test-Positive Screening Patients in Northern Italy. Dig Dis 2025; 43:235-245. [PMID: 39837308 DOI: 10.1159/000543307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2023] [Accepted: 09/10/2024] [Indexed: 01/23/2025]
Abstract
INTRODUCTION Colorectal non-polypoid lesions (NPLs) are flat, hard-to-detect, and mainly right-sided lesions. We aimed to assess the prevalence and endoscopic features of NPL lesions in a large cohort of screening patients in Northern Italy. METHODS Fecal immunochemical test (FIT)-positive subjects between 50 and 69 years old who had undergone at least a screening colonoscopy from March 2005 to December 2017 at the Endoscopy Unit of Ferrara were included. We selected only non-diminutive (>5 mm) and neoplastic polyps (i.e., adenomas, serrated adenomas, and carcinomas). Patients' demographics and polyps' endoscopic-histopathological data were collected. Categorical variables were compared using the Pearson's χ2 test and Fisher's exact test, while odd ratios and confidence intervals were estimated with univariate analysis. RESULTS A total of 6,676 FIT-positive subjects underwent 7,616 colonoscopies during the study period. Total lesions were 3,231, of which 133 were NPLs and among these 123 were neoplastic. The prevalence of NPLs among total lesions was 4.1%, while prevalence of neoplastic NPLs among total neoplastic lesions was 4.6%. The prevalence of NPLs and neoplastic NPLs among total colonoscopies was 1.7% and 1.6%, respectively. Neoplastic NPLs were more frequent between 60 and 64 years old (p = 0.03) and associated with other colonic polyps in subjects older than 60 years (p = 0.016). Cancerized NPLs were more likely in younger patients (50-59 years old, p = 0.04). CONCLUSIONS Prevalence of NPLs is low among the screening population, but NPLs are frequently associated with other colorectal polyps in patients older than 60 years and carry a higher risk of cancer in patients younger than 60 years old.
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Affiliation(s)
- Alessandro Pezzoli
- Gastroenterology Unit, Santa Maria della Misericordia Hospital, AULSS 5 Polesana, Rovigo, Italy
| | - Francesco Buttitta
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Caterina Palmonari
- Department of Public Health, Azienda Unità Sanitaria Locale di Ferrara, Ferrara, Italy
| | - Marzia Simoni
- Epidemiological Unit, CNR Institute of Clinical Physiology, Pisa, Italy
| | - Chiara Pierantoni
- Gastroenterology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico di Sant'Orsola, Bologna, Italy
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Alberto Merighi
- Department of Gastroenterology and Endoscopy, Sant'Anna Hospital, Ferrara, Italy
| | - Luigi Ricciardiello
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas at MD Anderson Cancer Center, Houston, Texas, USA
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Bara-Ledesma N, Viteri-Noel A, Lopez Rodriguez M, Stamatakis K, Fabregate M, Vazquez-Santos A, Gomez del Olmo V. Advances in Gene Therapy for Rare Diseases: Targeting Functional Haploinsufficiency Through AAV and mRNA Approaches. Int J Mol Sci 2025; 26:578. [PMID: 39859294 PMCID: PMC11765483 DOI: 10.3390/ijms26020578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/07/2025] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open
Abstract
Most rare diseases (RDs) encompass a diverse group of inherited disorders that affect millions of people worldwide. A significant proportion of these diseases are driven by functional haploinsufficiency, which is caused by pathogenic genetic variants. Currently, most treatments for RDs are limited to symptom management, emphasizing the need for therapies that directly address genetic deficiencies. Recent advancements in gene therapy, particularly with adeno-associated viruses (AAVs) and lipid nanoparticle-encapsulated messenger RNA (mRNA), have introduced promising therapeutic approaches. AAV vectors offer durable gene expression, extensive tissue tropism, and a safety profile that makes them a leading choice for gene delivery; however, limitations remain, including packaging size and immune response. In contrast, mRNA therapeutics, formulated in LNPs, facilitate transient protein expression without the risk of genomic integration, supporting repeated dosing and pharmacokinetic control, though with less long-term expression than AAVs. This review analyzes the latest developments in AAV and mRNA technologies for rare monogenic disorders, focusing on preclinical and clinical outcomes, vector design, and delivery challenges. We also address key regulatory and immunological considerations impacting therapeutic success. Together, these advancements in AAV and mRNA technology underscore a new era in RD treatment, providing innovative tools to target the genetic root of these diseases and expanding therapeutic approaches for patients who currently face limited medical options.
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Affiliation(s)
- Nuria Bara-Ledesma
- Internal Medicine Department, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain; (N.B.-L.)
- Faculty of Medicine and Health Sciences, Universidad de Alcalá (UAH), 28805 Alcalá de Henares, Spain
| | - Adrian Viteri-Noel
- Internal Medicine Department, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain; (N.B.-L.)
- Faculty of Medicine and Health Sciences, Universidad de Alcalá (UAH), 28805 Alcalá de Henares, Spain
| | - Monica Lopez Rodriguez
- Internal Medicine Department, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain; (N.B.-L.)
- Faculty of Medicine and Health Sciences, Universidad de Alcalá (UAH), 28805 Alcalá de Henares, Spain
| | - Konstantinos Stamatakis
- Department of Molecular Biology, Universidad Autónoma de Madrid, IRYCIS, 28049 Madrid, Spain
| | - Martin Fabregate
- Internal Medicine Department, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain; (N.B.-L.)
| | - Almudena Vazquez-Santos
- Internal Medicine Department, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain; (N.B.-L.)
| | - Vicente Gomez del Olmo
- Internal Medicine Department, Hospital Universitario Ramón y Cajal, IRYCIS, 28034 Madrid, Spain; (N.B.-L.)
- Faculty of Medicine and Health Sciences, Universidad de Alcalá (UAH), 28805 Alcalá de Henares, Spain
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Cortés-Torres EJ, Flores-Betancourt MDR, González-Ojeda A, Fuentes-Orozco C, Cervantes-Guevara G, Cervantes-Pérez E, Ramírez-Velázquez A, Hernández-Guzmán AK. [Association of T CD3+/T CD8+ lymphocytes in lymphatic and perineural infiltration in colorectal cancer]. REVISTA MEDICA DEL INSTITUTO MEXICANO DEL SEGURO SOCIAL 2025; 63:e6321. [PMID: 40267255 PMCID: PMC12068896 DOI: 10.5281/zenodo.14200044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2024] [Accepted: 10/01/2024] [Indexed: 04/25/2025]
Abstract
Background Colorectal cancer (CRC) is one of the most common and lethal neoplasia in the world. Key prognostic factors include lymphovascular and perineural infiltration, which negatively affect the disease by increasing the risk of metastasis. Studies indicate that low levels of CD8+ and CD3+ T cells may be associated with early metastasis. Objective To evaluate the sensitivity and specificity of preoperative serum cytotoxic T lymphocytes (CD8+ and CD3+) with lymphatic and perineural infiltration in colorectal cancer. Material and methods Prospective, cross-sectional, analytical study on cytotoxic T lymphocytes (CD8+ and CD3+). Descriptive statistics, measures of central tendency and dispersion for quantitative variables, frequency and percentage for qualitative variables were used. The samples obtained were associated with the presence of lymphovascular or perineural infiltration. Results 37 patients were included, with a mean age of 58 ± 10.9 years; 24 (64.8%) were female. 16 (43.2%) were diagnosed with malignant colon neoplasms, and 21 (56.7%) with malignant rectal tumors. Lymphovascular infiltration was found in 13 (35.1%) and 18 (48.6%) perineural infiltrates. CD8+ T lymphocyte levels were 219 cells/AL ± 140.5 cells/AL, and 16 (43.2%) had low levels. CD3+ T lymphocytes averaged with 943 cells/uL ± 640.4 cells/AL, and 16 (43.2%) had low levels. Conclusions Histopathologically we found an association between the serum level of CD3+ and CD8+ T cells and lymphovascular and perineural infiltration. Additional research has to be done to strengthen the results obtained.
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Affiliation(s)
- Edgar Joaquín Cortés-Torres
- Instituto Mexicano del Seguro Social, Centro Médico Nacional de Occidente, Hospital de Especialidades “Lic. Ignacio García Téllez”, Servicio de Cirugía Oncológica. Guadalajara, Jalisco, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - María del Refugio Flores-Betancourt
- Instituto Mexicano del Seguro Social, Centro Médico Nacional de Occidente, Hospital de Especialidades “Lic. Ignacio García Téllez”, Servicio de Cirugía Oncológica. Guadalajara, Jalisco, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - Alejandro González-Ojeda
- Instituto Mexicano del Seguro Social, Centro Médico Nacional de Occidente, Hospital de Especialidades “Lic. Ignacio García Téllez”, Unidad de Investigación Biomédica 02. Guadalajara, Jalisco, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - Clotilde Fuentes-Orozco
- Instituto Mexicano del Seguro Social, Centro Médico Nacional de Occidente, Hospital de Especialidades “Lic. Ignacio García Téllez”, Unidad de Investigación Biomédica 02. Guadalajara, Jalisco, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - Gabino Cervantes-Guevara
- Instituto Mexicano del Seguro Social, Centro Médico Nacional de Occidente, Hospital de Especialidades “Lic. Ignacio García Téllez”, Unidad de Investigación Biomédica 02. Guadalajara, Jalisco, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - Enrique Cervantes-Pérez
- Hospital Civil de Guadalajara Fray Antonio Alcalde, Departamento de Medicina Interna. Guadalajara, Jalisco, MéxicoHospital Civil de Guadalajara Fray Antonio AlcaldeMéxico
| | - Alejandro Ramírez-Velázquez
- Instituto Mexicano del Seguro Social, Centro Médico Nacional de Occidente, Hospital de Especialidades “Lic. Ignacio García Téllez”, Unidad de Investigación Biomédica 02. Guadalajara, Jalisco, MéxicoInstituto Mexicano del Seguro SocialMéxico
| | - Ana Karen Hernández-Guzmán
- Instituto Mexicano del Seguro Social, Centro Médico Nacional de Occidente, Hospital de Especialidades “Lic. Ignacio García Téllez”, Departamento de Cirugía General. Guadalajara, Jalisco, MéxicoInstituto Mexicano del Seguro SocialMéxico
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Zhou Z, Kleis L, Depetris-Chauvin A, Jaskulski S, Damerell V, Michels KB, Gigic B, Nöthlings U, Panagiotou G. Beneficial microbiome and diet interplay in early-onset colorectal cancer. EMBO Mol Med 2025; 17:9-30. [PMID: 39653811 PMCID: PMC11730345 DOI: 10.1038/s44321-024-00177-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 10/30/2024] [Accepted: 11/08/2024] [Indexed: 01/15/2025] Open
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide. Although the risk of developing CRC increases with age, approximately 10% of newly diagnosed cases occur in individuals under the age of 50. Significant changes in dietary habits in young adults since industrialization create a favorable microenvironment for colorectal carcinogenesis. We aim here to shed light on the complex interplay between diet and gut microbiome in the pathogenesis and prevention of early-onset CRC (EO-CRC). We provide an overview of dietary risk factors associated with EO-CRC and contrast them with the general trends for CRC. We delve into gut bacteria, fungi, and phages with potential benefits against CRC and discuss the underlying molecular mechanisms. Furthermore, based on recent findings from human studies, we offer insights into how dietary modifications could potentially enhance gut microbiome composition to mitigate CRC risk. All together, we outline the current research landscape in this area and propose directions for future investigations that could pave the way for novel preventive and therapeutic strategies.
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Affiliation(s)
- Zhengyuan Zhou
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), Jena, Germany
| | - Linda Kleis
- Institute of Nutritional and Food Sciences-Nutritional Epidemiology, University of Bonn, Friedrich-Hirzebruch-Allee 7, 53115, Bonn, Germany
| | - Ana Depetris-Chauvin
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), Jena, Germany
| | - Stefanie Jaskulski
- Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Victoria Damerell
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Karin B Michels
- Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany
| | - Biljana Gigic
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Ute Nöthlings
- Institute of Nutritional and Food Sciences-Nutritional Epidemiology, University of Bonn, Friedrich-Hirzebruch-Allee 7, 53115, Bonn, Germany.
| | - Gianni Panagiotou
- Department of Microbiome Dynamics, Leibniz Institute for Natural Product Research and Infection Biology (Leibniz-HKI), Jena, Germany.
- Friedrich Schiller University, Faculty of Biological Sciences, Jena, Germany.
- Friedrich Schiller University, Jena University Hospital, Jena, Germany.
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Li X, Xiao X, Wu Z, Li A, Wang W, Lin R. Global, regional, and national burden of early-onset colorectal cancer and projection to 2050: An analysis based on the Global Burden of Disease Study 2021. Public Health 2025; 238:245-253. [PMID: 39700867 DOI: 10.1016/j.puhe.2024.12.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 11/07/2024] [Accepted: 12/08/2024] [Indexed: 12/21/2024]
Abstract
OBJECTIVES Early-onset colorectal cancer (EO-CRC) is becoming increasingly concerning due to its impact on individuals under 50 years old. We explored the burden of EO-CRC to provide information for planning effective management and prevention strategies. STUDY DESIGN We conducted secondary analyses to assess the burden of EO-CRC using data from GBD 2021. METHODS The incidence, prevalence, deaths, disability-adjusted life years (DALYs) and their rates across 204 countries and territories were obtained from GBD 2021 database. The estimated annual percentage change (EAPC) calculation was used to assess temporal trends in these metrics. Additionally, we reported the proportion of DALYs attributable to risk factors and projected future disease burden till 2050. RESULTS The global number of new EO-CRC cases increased from 107,310 in 1990 to 211,890 in 2021. Both age-standardized incidence rate (ASIR) and prevalence rate (ASPR) of EO-CRC showed overall increases over the study period (ASIR: EAPC = 0.96 (0.9-1.02), ASPR: EAPC = 1.5 (1.44-1.55)). However, a decline in ASIR and ASPR was observed in 2020 and 2021. Males consistently showed higher EO-CRC indicators compared to females. Furthermore, projections indicated that deaths and DALYs cases are likely to fluctuate but generally increase by 2050, reaching 85,602 and 4,283,093, respectively. CONCLUSIONS The global impact of EO-CRC has increased significantly from 1990 to 2021, revealing notable variations across SDI regions, countries, age groups, and sexes. Besides, deaths and DALYs are predicted to rise by 2050. These results highlight the importance of implementing measures to address the growing burden of EO-CRC globally.
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Affiliation(s)
- Xinyi Li
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xueyan Xiao
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zenghong Wu
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Anni Li
- School of Public Health, Key Lab of Public Health Safety of the Ministry of Education and NHC Key Lab of Health Technology Assessment, Fudan University, Shanghai, China
| | - Weijun Wang
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Rong Lin
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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Liu FH, Lin XC, Liu YW, Zhang TT, Zhang YB, Xie ZL, Zhan Y, Hu P. Harmine inhibits the proliferation and migration and promotes the apoptosis of colon cancer cells via inhibition of the FAK/AKT and ERK 1/2/CREB signaling pathways. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2025; 27:75-87. [PMID: 39001813 DOI: 10.1080/10286020.2024.2361767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 05/23/2024] [Accepted: 05/23/2024] [Indexed: 07/15/2024]
Abstract
Harmine is present in a variety of medicinal plants, and its effects on colon cancer cells remain unclear. Here, we found that harmine exhibited significant inhibitory effects on the proliferation of colon cancer cells by inhibiting the phosphorylation levels of the FAK/AKT and ERK1/2/CREB. Furthermore, harmine also inhibited the migration of colon cancer cells and suppressed the expression levels of MMP-2, MMP-9, and VEGF. Additionally, harmine-induced apoptosis in colon cancer cells by regulating the expression of Bcl-2 and Bax. In conclusion, our findings suggest that harmine exerts a significant inhibitory effect on the development of colon cancer cells.
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Affiliation(s)
- Fu-Hong Liu
- Institute of Translational Medicine, Nanchang University, Nanchang 330001, China
| | - Xing-Cheng Lin
- Institute of Translational Medicine, Nanchang University, Nanchang 330001, China
| | - Yu-Wei Liu
- Institute of Translational Medicine, Nanchang University, Nanchang 330001, China
| | - Tian-Tian Zhang
- Institute of Translational Medicine, Nanchang University, Nanchang 330001, China
| | - Yang-Bo Zhang
- Department of Neurology, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
| | - Zhuo-Long Xie
- Joint Program of Nanchang University and Queen Mary University of London, Nanchang 330001, China
| | - Yuan Zhan
- Department of Pathology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
| | - Ping Hu
- Institute of Translational Medicine, Nanchang University, Nanchang 330001, China
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Wang J, He S, Cao M, Teng Y, Li Q, Tan N, Wu Y, Zuo T, Li T, Zheng Y, Xia C, Chen W. Global, regional, and national burden of colorectal cancer, 1990 -2021: An analysis from global burden of disease study 2021. Chin J Cancer Res 2024; 36:752-767. [PMID: 39802900 PMCID: PMC11724172 DOI: 10.21147/j.issn.1000-9604.2024.06.12] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 12/13/2024] [Indexed: 01/16/2025] Open
Abstract
Objective Data on the global, regional and national changes in the trends of colorectal cancer (CRC) are analyzed to understand the trends in its burden, in order to assist policymakers in allocating healthcare resources and developing prevention and control strategies. Methods This study analyzed trends in age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and disability-adjusted life years (DALYs) for CRC from 1990 to 2021 using data from the Global Burden of Disease (GBD) 2021 database. The trends of burden and effectiveness of control strategies were assessed using jointpoint regression analysis, decomposition analysis and frontier analysis. Results Globally, the ASMR and age-standardized DALYs for CRC have shown a declining trend, but the ASIR was still increasing. The number of new cases of CRC in 2021 was higher in males than in females, the values were 1,263.46 thousands [95% confidence interval (95% CI): 1,146.50, 1,400.38] vs. 930.68 thousands (95% CI: 824.67, 1,017.65). The change in DALYs was mainly due to population growth (111.42%). The high socio-demographic index (SDI) region had an ASIR of 40.52 (95% CI: 37.45, 42.45), and the low SDI region had an ASIR of 7.39 (95% CI: 6.65, 8.19). The ASIR for CRC showed an upward trend in all SDI regions before age of 40 years. Among the four world regions, only America showed a downward trend in ASIR, with an estimated annual percentage change (EAPC) of -0.62 (95% CI: -0.71, -0.53). Among the 204 countries and territories, Netherlands, Monaco, and Bermuda were the top 3 countries with the highest ASIR in 2021. In the frontier analysis of DALYs, the 10 countries with the longest effective distances all had SDI levels above 0.70. Conclusions Although ASMR and age-standardized DALYs are declining, ASIR is still increasing globally and in many regions. The burden of CRC varies significantly across the globe, and more targeted screening strategies and prevention measures are needed to address the problem of CRC.
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Affiliation(s)
- Jiachen Wang
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Siyi He
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Mengdi Cao
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yi Teng
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Qianru Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Nuopei Tan
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yujie Wu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Tingting Zuo
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Tianyi Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Yuanjie Zheng
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Changfa Xia
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wanqing Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Nhung PTT, Le HTT, Nguyen QH, Huyen DT, Quyen DV, Song LH, Van Thuan T, Tran TTT. Identifying fecal microbiota signatures of colorectal cancer in a Vietnamese cohort. Front Microbiol 2024; 15:1388740. [PMID: 39777151 PMCID: PMC11704495 DOI: 10.3389/fmicb.2024.1388740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 12/04/2024] [Indexed: 01/11/2025] Open
Abstract
Background Colorectal cancer (CRC) is among the top three causes of global cancer mortality. In Vietnam, CRC is the third leading cause of death in women and the fourth cause of cancer mortality in men. A large number of metagenomic studies have reported the relationship between altered composition and function of the gut microbiota with CRC, but this relationship in low- and middle-income countries including Vietnam (with an estimated population of 100.3 million people in 2023, ranking 16th largest country by population in the world) is not well-explored. Methods We collected clinical data and fecal samples from 43 CRC patients and 44 healthy control subjects. The total community DNA of microorganisms was extracted from the fecal samples and analyzed for microbiota composition using Illumina MiSeq amplicon sequencing targeting the V3-V4 region of the 16S rRNA gene. Results We identified a significant difference in the overall fecal microbiota composition between CRC patients and healthy controls, and we detected several CRC-associated microbial signatures in fecal samples of Vietnamese patients with CRC, which overlapped with signatures from other countries and meta-analyses. Although patients with (n = 8) and without (n = 35) type 2 diabetes (T2D) exhibited distinct gut microbiota composition compared to healthy controls, increased relative abundances of putatively pathogenic species including Parvimonas micra, Peptostreptococcus stomatis, and Prevotella intermedia were consistent biomarkers for CRC. In contrast, several health-associated species were significantly depleted in CRC patients such as Lactobacillus johnsonii and Bifidobacterium longum in CRC/non-T2D patients, Ruminococcus species, Bacteroides uniformis, and Phascolarctobacterium faecium in CRC/T2D patients, and Butyricicoccus pullicaecorum in both CRC groups combined. Conclusion Our findings confirm alterations in gut microbiota composition in CRC in a pilot Vietnamese cohort and highlight several gut microbial taxa that may have inhibitory or driver roles in CRC. This and future studies will enable the development of cancer diagnostics and treatment strategies for CRC in Vietnam, with a focus on targeting the microbiota.
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Affiliation(s)
- Pham Thi Tuyet Nhung
- Hanoi Medical University, Hanoi, Vietnam
- 108 Military Central Hospital, Hanoi, Vietnam
| | - Hang Thi Thu Le
- Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam
| | - Quang Huy Nguyen
- Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam
| | - Dao Thi Huyen
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
| | - Dong Van Quyen
- Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam
- Molecular Microbiology Lab, Institute of Biotechnology (IBT), Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam
| | - Le Huu Song
- 108 Military Central Hospital, Hanoi, Vietnam
- Vietnamese-German Center for Medical Research (VG-CARE), Hanoi, Vietnam
| | | | - Tam Thi Thanh Tran
- Department of Life Sciences, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam
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Nguyen DK, Kang MJ, Oh SJ, Park HJ, Kim SH, Yu JH, Lee Y, Lee HS, Yang JW, Seo Y, Ahn JS, Kim HS. Parvimonas micra-polarized M2-like tumor-associated macrophages accelerate colorectal cancer development via IL-8 secretion. Anim Cells Syst (Seoul) 2024; 29:24-34. [PMID: 39777026 PMCID: PMC11703389 DOI: 10.1080/19768354.2024.2442401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 10/27/2024] [Accepted: 11/29/2024] [Indexed: 01/11/2025] Open
Abstract
Parvimonas micra (Pm), a periodontal pathogen, has been implicated in the impairment of anti-tumor responses in colorectal cancer (CRC). The tumor microenvironment in CRC involves tumor-associated macrophages (TAMs), which are pivotal in modulating tumor-associated immune responses. The polarization of TAMs towards an M2-like phenotype promotes CRC progression by suppressing the immune system. However, the mechanisms by which Pm affects the progression of CRC remain inadequately elucidated. In this study, we explored the impact of Pm infection on CRC cell characteristics, including proliferation, chemoresistance, migration, and macrophage polarization. We found that Pm-infected THP-1-derived macrophages exhibited elevated interleukin-10 levels, a well-established M2 marker. Conditioned media from Pm-treated THP-1 cells significantly enhanced CRC cell proliferation, cisplatin resistance, and migration, and interleukin-8 was identified as a key factor. Consistent with the in vitro results, an azoxymethane/dextran sodium sulfate mouse model treated with oral Pm showed accelerated CRC tumor growth. These results offer mechanistic insights into the influence of Pm infection on tumor microenvironment in CRC through M2-like macrophage polarization. The identified pathways may serve as potential targets for therapeutic interventions for CRC.
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Affiliation(s)
- Dang Khoa Nguyen
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Min-Jung Kang
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Su-Jeong Oh
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Hee-Jeong Park
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Seong Hui Kim
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Jeong Hyun Yu
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Yunji Lee
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Hyeon Seo Lee
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Ji Won Yang
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Yoojin Seo
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Ji-Su Ahn
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
| | - Hyung-Sik Kim
- Department of Oral Biochemistry, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, Republic of Korea
- Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan, Republic of Korea
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de Moraes FCA, Moretti NR, Sano VKT, Ngan CWT, Burbano RMR. Genomic mosaicism in colorectal cancer and polyposis syndromes: a systematic review and meta-analysis. Int J Colorectal Dis 2024; 39:201. [PMID: 39674994 DOI: 10.1007/s00384-024-04776-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/05/2024] [Indexed: 12/17/2024]
Abstract
BACKGROUND Colorectal cancer (CRC) and polypoid syndromes are significant public health concerns, with somatic mosaicism playing a crucial role in their genetic diversity. This study aimed to investigate the prevalence and impact of somatic mosaicism in these conditions. METHODS A search was conducted using PubMed, Scopus, and Web of Sciences to identify studies evaluating mosaicism in patients with CRC or polyposis syndromes. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to determine prevalence rates. Statistical analyses were performed using R software 4.3. RESULTS A total of 27 studies, encompassing 2272 patients, were included in the analysis. Of these, 108 patients exhibited somatic mosaicism, resulting in an overall prevalence of 8.79% (95% CI 5.1 to 14.70%, I2 = 85; p < 0.01). Subgroup analyses revealed a significantly higher prevalence of mosaicism in patients with APC mutations (OR 13.43%, 95% CI 6.36 to 26.18%, I2 = 87; p < 0.01). Additionally, mosaicism in MLH1 and MSH2 genes was observed at rates of 2.75% (95% CI 1.20 to 6.18%) and 9.69% (95% CI 2.98 to 27.24%), respectively. CONCLUSIONS Our findings support the growing recognition of mosaicism as a critical factor in CRC susceptibility and underscore the importance of incorporating mosaicism screening into routine genetic testing for at-risk patients.
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Angelakas A, Christodoulou T, Kamposioras K, Barriuso J, Braun M, Hasan J, Marti K, Misra V, Mullamitha S, Saunders M, Cook N. Is early-onset colorectal cancer an evolving pandemic? Real-world data from a tertiary cancer center. Oncologist 2024; 29:e1680-e1691. [PMID: 39359067 PMCID: PMC11630742 DOI: 10.1093/oncolo/oyae239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Accepted: 08/07/2024] [Indexed: 10/04/2024] Open
Abstract
BACKGROUND Early onset Colorectal Cancer (EOCRC), defined as those diagnosed under the age of 50, has been increasing rapidly since 1970. UK data on EOCRC are currently limited and better understanding of the condition is needed. MATERIALS AND METHODS A single-center retrospective study of patients with EOCRC treated over 9 years (2013-2021) at a large UK cancer center was performed. Clinicopathological features, risk factors, molecular drivers, treatment, and survival were analyzed. RESULTS In total, 203 patients were included. A significant increase in cases was reported from 2018-2019 (n = 33) to 2020-2021 (n = 118). Sporadic EOCRC accounted for 70% of cases and left-sided tumors represented 70.9% (n = 144). Median duration of symptoms was 3 months, while 52.7% of the patients had de-novo metastatic disease. Progression-free survival after first-line chemotherapy was 6 months (95% CI, 4.85-7.15) and median overall survival (OS) was 38 months (95% CI, 32.86-43.14). In the advanced setting, left-sided primary tumors were associated with a median OS benefit of 14 months over right-sided primaries (28 vs 14 months, P = .009). Finally, primary tumor resection was associated with median OS benefit of 21 months compared with in situ tumors (38 vs 17 months, P < .001). CONCLUSIONS The incidence of EOCRC is increasing, and survival outcomes remain modest. Raising public awareness and lowering the age for colorectal cancer screening are directions that could improve EOCRC clinical outcomes. There is also a need for large prospective studies to improve the understanding of the nature of EOCRC and the best therapeutic approaches.
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Affiliation(s)
- Angelos Angelakas
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Thekla Christodoulou
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Konstantinos Kamposioras
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Jorge Barriuso
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Michael Braun
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Jurjees Hasan
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Kalena Marti
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Vivek Misra
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Saifee Mullamitha
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Mark Saunders
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, United Kingdom
| | - Natalie Cook
- The Christie NHS Foundation Trust and Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M20 4BX, United Kingdom
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Brinkman MT, Crofts S, Green H. The use of nutrigenomics and nutritional biomarkers with standard care of long-term recurrent metastatic rectal cancer: a case report. Front Oncol 2024; 14:1451675. [PMID: 39687889 PMCID: PMC11646835 DOI: 10.3389/fonc.2024.1451675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 11/07/2024] [Indexed: 12/18/2024] Open
Abstract
Introduction Distant metastases following standard treatment for locally advanced rectal cancer (LARC) are typically associated with poor disease-free survival. We report on a 52-year-old Australian male of Dutch ancestry with no family history of colorectal cancer or significant medical history who experienced bleeding per rectum for several months prior to a colonoscopy in July 2010. He was subsequently diagnosed with Stage IIb LARC. Case presentation Despite treatment with curative intent, a distant recurrence to his left lung was detected in May 2012, upstaging him to Stage IV rectal cancer. He had repeated distant metastatic recurrences over the next 8 years, and treatment included multiple surgeries, chemotherapies, radiation treatments, a "watch and wait" period of 20 months, and personalised dietary management. Genetic and nutrigenomic testing identified that the case had KRAS and MTHFR mutations. As part of his dietary management, the case also had his levels of folate, vitamin B12, and vitamin D regularly monitored because of his genetic predisposition and history of deficiency for these key nutrients. Apart from changes in his CEA levels, sudden increases in the patient's folate levels, inconsistent with dietary exposures preceded detection of each new distant recurrence, with significant decreases in the levels at the next follow-up measurement. Conclusion A multimodal approach to this patient's management appeared to contribute to his long-term survival of nearly 10 years from the initial diagnosis. Multidisciplinary management, including the use of additional biomarkers, may enhance survival rates in other similar cases with advanced disease resistant to differing therapies, and with potentially poor prognosis.
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Affiliation(s)
- Maree T. Brinkman
- Department of Clinical Studies and Nutritional Epidemiology, Nutrition Biomed Research Institute, Melbourne, VIC, Australia
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Zhang D, Liu S, Li Z, Shen M, Li Z, Wang R. Burden of gastrointestinal cancers among adolescent and young adults in Asia-Pacific region: trends from 1990 to 2019 and future predictions to 2044. Ann Med 2024; 56:2427367. [PMID: 39551644 PMCID: PMC11571724 DOI: 10.1080/07853890.2024.2427367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 10/13/2024] [Accepted: 10/21/2024] [Indexed: 11/19/2024] Open
Abstract
BACKGROUND Gastrointestinal cancer is a significant cause of cancer incidence and mortality. Nevertheless, the epidemiology of the burden among adolescents and young adults (AYAs, aged 15-39 years) remains limited in the Asia-Pacific region, despite the region's significant population. This study aims to explore the gastrointestinal cancer burden among AYAs in the Asia-Pacific region for the year 2019, while also analysing trends from 1990 to 2019 and projecting future trends up to 2044. METHODS Annual case numbers, age-standardized rates of incidence, death, and disability-adjusted life-years (DALYs) and their estimated annual percentage changes (EAPCs) for gastrointestinal cancers were derived from the Global Burden of Disease, Injuries, and Risk Factors Study 2019. Trends over the next 25 years have also been predicted. RESULTS In 2019, there were 117,714 incident cases, 61,578 deaths and 3,483,053 DALYs due to gastrointestinal cancers in the Asia-Pacific region, accounting for 68.5%, 67.6% and 72.4%, respectively, of global gastrointestinal cancers in this population. The highest age-standardized rates occurred in countries with a middle Socio-demographic Index. From 1990 to 2019, there was a decline in the age-standardized rates of incidence, death and DALY attributed to gastrointestinal cancers, with EAPC of -1.10, -2.48 and -2.44, respectively. These rates are expected to stabilize over 25 years, with notable variations in individual gastrointestinal cancers. CONCLUSIONS Gastrointestinal cancers among AYAs in the Asia-Pacific region have posed a significant burden over the past 30 years and are expected to persist in the coming years.
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Affiliation(s)
- Decai Zhang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan Province, China
| | - Shaojun Liu
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan Province, China
| | - Zhaoqi Li
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan Province, China
| | - Minxue Shen
- Department of Social Medicine and Health Management, Xiangya School of Public Health, Central South University, Changsha, China
| | - Zihao Li
- Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, China
- The First People’s Hospital Of Changde City, Changde City, Hunan Province, China
| | - Rui Wang
- Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China
- Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan Province, China
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Nawras Y, Merza N, Beier K, Dakroub A, Al-Obaidi H, Al-Obaidi AD, Amatul-Raheem H, Bahbah E, Varughese T, Hosny J, Hassan M, Kobeissy A. Temporal Trends in Racial and Gender Disparities of Early Onset Colorectal Cancer in the United States: An Analysis of the CDC WONDER Database. J Gastrointest Cancer 2024; 55:1511-1519. [PMID: 39352432 PMCID: PMC11464567 DOI: 10.1007/s12029-024-01096-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/20/2024] [Indexed: 10/10/2024]
Abstract
BACKGROUND The mortality rates of early-onset colorectal cancer (EOCRC) have surged globally over the past two decades. While the underlying reasons remain largely unknown, understanding its epidemiology is crucial to address this escalating trend. This study aimed to identify disparities potentially influencing these rates, enhancing risk assessment tools, and highlighting areas necessitating further research. METHODS Using the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) database, this study assessed EOCRC mortality data from 2012 to 2020. Individuals under 50 years who succumbed to EOCRC were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Data interpretation and representation were performed using R 4.2.2 software. RESULTS Between 2012 and 2020, EOCRC mortality rates fluctuated marginally between 1.7 and 1.8 per 100,000. Male mortality rates increased from 1.9 to 2.0 per 100,000, while female rates varied between 1.5 and 1.6 per 100,000. Significant variations were observed across age groups, with the 40-49 years category experiencing an increase from 6.34 (2012) to 6.94 (2020) per 100,000. Racial category-based data revealed the highest mortality rates among African Americans. Geographically, Mississippi and Alabama exhibited elevated mortality rates. Age-adjusted mortality rate (AAMR) assessments indicated a marked decline for both genders from 2012 to 2020, with consistently higher rates for men. CONCLUSION The findings highlight the evolving landscape of EOCRC mortality, revealing significant gender, age, and racial disparities. These results underscore the urgent need for tailored health strategies and intensified research efforts targeting these disparities.
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Affiliation(s)
- Yusuf Nawras
- University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Nooraldin Merza
- Department of Internal Medicine, The University of Toledo, Toledo, OH, USA.
| | - Katie Beier
- University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Aya Dakroub
- University of Toledo College of Medicine and Life Sciences, Toledo, OH, USA
| | - Hasan Al-Obaidi
- Department of Medicine, Jamaica Hospital Medical Center, Queens, NY, USA
| | | | | | - Eshak Bahbah
- Department of Internal Medicine, Al Azhar University, Cairo, Egypt
| | - Tony Varughese
- Department of Internal Medicine, Hackensack University Medical Center, Hackensack, NJ, USA
| | - Jerome Hosny
- Department of Internal Medicine, The University of Balamand, Balamand, Lebanon
| | - Mona Hassan
- Department of Gastroenterology, The University of Toledo, Toledo, OH, USA
| | - Abdallah Kobeissy
- Department of Gastroenterology, The University of Toledo, Toledo, OH, USA
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Carbajal-López B, Coronel-Hernández J, Herrera M, Ruiz-Garcia E, Miyagui-Adame SM, Diaz-Romero C, Madrigal-Santillán EO, Esponda-Mendoza PM, Pérez-Plasencia C, Calderillo-Ruiz G. Age as a Predictor of Overall Survival in Colorectal Cancer. Diagnostics (Basel) 2024; 14:2550. [PMID: 39594216 PMCID: PMC11592752 DOI: 10.3390/diagnostics14222550] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Revised: 11/08/2024] [Accepted: 11/10/2024] [Indexed: 11/28/2024] Open
Abstract
BACKGROUND The diagnosis of colorectal cancer (CRC) at early ages has become a challenging trend for oncology due to high rates of mortality worldwide. The correlation of clinical features with young-age prognosis in CRC remains unclear. Therefore, we aimed to describe the clinicopathological features and their impact on the overall survival of young Mexican adults diagnosed with CRC treated in the National Cancer Institute. METHODS This was a retrospective, observational study. The included patients were treated at the National Cancer Institute between 2004 and 2020. The statistical analyses comprised the X2 and t tests, Kaplan-Meier, log rank, and Cox regression. Statistical significances were assessed when p was bilaterally < 0.05. RESULTS A total of 3652 patients diagnosed with CRC attended the National Cancer Institute. Cases of early onset of CRC increased over the 16 years under study, with significant differences between the median age, from 57 in 2004 to 55 years old in 2020 (F = 5.49; gl: 12 p = 0.019). For this analysis, the population was divided in three groups: young (≤30 years), adults (31-70), and elderly (>70). The young population was mostly composed of men (62%; (n = 63), (p = 0.020), with high rates of metastatic disease (44%) (p = 0.001) and right-side tumors (57%), (p = 0.046), and with 44% with a moderate grade (p = 0.750). According to the overall survival (OS) analysis, the median OS was 29 months for young, versus 170 months for adult and 56 months for elderly patients (p <0.001, HR 1.53, 95% CI 1.11-2.10). A sub-analysis was performed considering only patients with metastatic disease. The median OS was 12 months for young, versus 17 and 9 months for adults and elderly (p = 0.08, HR 1.27, 95% CI 1.02-1.46). CONCLUSIONS CRC diagnosis in the young population is increasing due unhealthy lifestyle habits and lack of screening. This population have clinical features of bad prognosis, such as left side, poor grade differentiation, and metastatic disease, precluding prognosis and OS.
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Affiliation(s)
- Berenice Carbajal-López
- Unidad Funcional de gastroenterología, Instituto Nacional de Cancerología, Tlalpan 14080, Mexico; (B.C.-L.); (M.H.); (S.M.M.-A.); (C.D.-R.)
| | | | - Marytere Herrera
- Unidad Funcional de gastroenterología, Instituto Nacional de Cancerología, Tlalpan 14080, Mexico; (B.C.-L.); (M.H.); (S.M.M.-A.); (C.D.-R.)
| | - Erika Ruiz-Garcia
- Dirección de Docencia y Laboratorio de Medicina Traslacional, Instituto Nacional de Cancerología, Tlalpan 14080, Mexico;
| | - Sayako M. Miyagui-Adame
- Unidad Funcional de gastroenterología, Instituto Nacional de Cancerología, Tlalpan 14080, Mexico; (B.C.-L.); (M.H.); (S.M.M.-A.); (C.D.-R.)
| | - Consuelo Diaz-Romero
- Unidad Funcional de gastroenterología, Instituto Nacional de Cancerología, Tlalpan 14080, Mexico; (B.C.-L.); (M.H.); (S.M.M.-A.); (C.D.-R.)
| | - Eduardo Osiris Madrigal-Santillán
- Laboratorio de Medicina de la Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico 11340, Mexico;
| | - Priscila Morales Esponda-Mendoza
- Faculty of Medicine, Universidad Nacional Autónoma de México, Av. Universidad 3004, Copilco Universidad, Coyoacán, Ciudad de Mexico 04510, Mexico;
| | | | - Germán Calderillo-Ruiz
- Unidad Funcional de gastroenterología, Instituto Nacional de Cancerología, Tlalpan 14080, Mexico; (B.C.-L.); (M.H.); (S.M.M.-A.); (C.D.-R.)
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Zhang J, Ou D, Xie A, Chen D, Li X. Global burden and cross-country health inequalities of early-onset colorectal cancer and its risk factors from 1990 to 2021 and its projection until 2036. BMC Public Health 2024; 24:3124. [PMID: 39533235 PMCID: PMC11556159 DOI: 10.1186/s12889-024-20624-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2024] [Accepted: 11/05/2024] [Indexed: 11/16/2024] Open
Abstract
PURPOSE To explore the worldwide, regional, and country-specific burden of early-onset colorectal cancer (EO-CRC) and identify its associated risk factors between 1990 and 2021, and to project its incidence and mortality rates for 2036. METHODS We acquired data on EO-CRC categorized by gender, socio-demographic index (SDI), and risk factors based on the Global Burden of Disease (GBD) Study 2021. Joinpoint regression analysis was utilized to explore the variation in disease burden. The autoregressive integrated moving average (ARIMA) model was performed to forecast the disease burden up to 2036. RESULTS Globally, the incidence rate, prevalence rate, mortality rate, and disability-adjusted life years (DALYs) rate of EO-CRC were estimated at 5.37 (95%UI: 4.91 to 5.86)/100,000, 34 (95%UI: 30.96 to 37.35)/100,000, 2.01 (95%UI: 1.84 to 2.19)/100,000, and 101.37 (95%: 92.85 to 110.18)/100,000 in 2021. The prevalence and incidence rates of EO-CRC showed an ascending trajectory, whilst the DALYs and mortality rates demonstrated a downward trajectory between 1990 to 2021. The high-middle SDI regions and East Asia exhibited the highest EO-CRC burden among the five SDI regions and 21 GBD regions respectively. A low-whole-grains diet was the chief risk factor contributing to EO-CRC. It was predicted that the age-standardized rate (ASR) of EO-CRC incidence would increase by 5.56%, while the ASR of mortality would decrease by 13.9% globally until 2036. CONCLUSION The current and future global burden of EO-CRC is heavy and varies significantly across different regions and countries.
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Affiliation(s)
- Jinhai Zhang
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57, Changping Road, Shantou, Guangdong Province, 515041, China
| | - Dehua Ou
- Department of Urology, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China
| | - Aosi Xie
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57, Changping Road, Shantou, Guangdong Province, 515041, China
| | - Diqun Chen
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57, Changping Road, Shantou, Guangdong Province, 515041, China
| | - Xinxin Li
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Shantou University Medical College, No. 57, Changping Road, Shantou, Guangdong Province, 515041, China.
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Zinkeng A, Taylor FL, Cheong SH, Song H, Merchant JL. Early Onset Colorectal Cancer: Molecular Underpinnings Accelerating Occurrence. Cell Mol Gastroenterol Hepatol 2024; 19:101425. [PMID: 39510499 PMCID: PMC11731505 DOI: 10.1016/j.jcmgh.2024.101425] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 10/28/2024] [Accepted: 10/28/2024] [Indexed: 11/15/2024]
Abstract
The onset of colorectal cancer (CRC) in patients younger than 50 continues to rapidly increase. This study highlights the epidemiologic changes, risk factors, clinical characteristics, and molecular profiles prevalent in early onset CRC patients, and identifies key areas for future research. It has been noted that only a small fraction of early onset CRC cases is attributed to known hereditary mutations and fit the canonical pathway of late-onset colorectal cancer development. To highlight this, we review the genetic and epigenetic modifications specific to early onset CRC. We also discuss the synergetic effect of single-nucleotide polymorphisms and environmental factors on the early onset of CRC. Additionally, we discuss the potential of noninvasive biomarker assays to enhance early detection, screening, diagnosis, and prognostic outcome predictions.
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Affiliation(s)
- Atehkeng Zinkeng
- Medical Scientist Training Program, University of Arizona College of Medicine, Tucson, Arizona
| | | | | | | | - Juanita L Merchant
- Department of Medicine, University of Arizona College of Medicine, Tucson, Arizona.
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