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Sandhu S, Blandon C, Kumar S. Evaluating Risk Factors for Early-Onset Colorectal Cancer in a Large, Prospective Cohort. Dig Dis Sci 2025:10.1007/s10620-025-09055-2. [PMID: 40234296 DOI: 10.1007/s10620-025-09055-2] [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: 12/11/2024] [Accepted: 04/09/2025] [Indexed: 04/17/2025]
Abstract
BACKGROUND Despite the worrisome rise of early-onset colorectal cancer (EOCRC), risk factors have not been definitively established. We use a large, granular database to evaluate risk factors for EOCRC, investigate differences in associations with EOCRC and later-onset CRC (LOCRC), and compare metrics of accelerated aging, a hypothesized driver of EOCRC. METHODS This was a case-control analysis within the UK Biobank. Risk factors for each cancer were identified and compared, including aging measures (chronological age, telomere length, PhenoAge, and homeostatic dysregulation). RESULTS A total of 31,164 persons were matched. We found an increased risk of EOCRC with PRS (OR 1.53; 95% CI 1.19-1.97; p < 0.001). LOCRC was associated with increasing PRS (OR 1.48; 95% CI 1.44 - 1.53; p < 0.001), increasing waist-to-hip ratio (OR 5.81; 95% CI 3.25 - 10.38; p < 0.001), family history of CRC (OR 1.27; 95% CI 1.16 - 1.40; p < 0.001), and history of smoking (OR 1.11; 95% CI 1.03 - 1.19; p = 0.01). Male sex and prior CRC screening were associated with reduced risk of LOCRC. The inclusion of PhenoAge as the measure of aging demonstrated the best model fit for both EOCRC and LOCRC. For each year that PhenoAge exceeded chronological age, the odds of EOCRC increased by 7%, while odds of LOCRC only increased by 1%. CONCLUSIONS Within this study, we find that genetic risk variants are a significant driver of EOCRC risk. Accelerated aging appears to be associated with increased risk of both EOCRC and LOCRC, and measures such as PhenoAge warrant continued study.
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Affiliation(s)
- Sunny Sandhu
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, 1120 NW 14th St, Locator Code C-240, Miami, FL, 33136, USA
| | - Catherine Blandon
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, 1120 NW 14th St, Locator Code C-240, Miami, FL, 33136, USA
| | - Shria Kumar
- Division of Digestive Health and Liver Diseases, Department of Medicine, Miller School of Medicine at the University of Miami, 1120 NW 14th St, Locator Code C-240, Miami, FL, 33136, USA.
- Sylvester Comprehensive Cancer Center, Miller School of Medicine at the University of Miami, 1120 NW 14th St, Locator Code C-240, Miami, FL, 33136, USA.
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Park H, Kim JI, Choi CH, Park JM, Kang S, Jin H, Chie EK, Son J. Evaluation of internal scatter contribution to gonadal dose in colorectal radiotherapy. Biomed Phys Eng Express 2025; 11:035009. [PMID: 40101302 DOI: 10.1088/2057-1976/adc1cf] [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: 10/23/2024] [Accepted: 03/18/2025] [Indexed: 03/20/2025]
Abstract
Colorectal cancer is among the most common cancers in terms of both incidence and mortality. External beam radiotherapy is frequently used to treat colorectal cancer. In colorectal radiotherapy, the gonad is considered as an organ that must be spared owing to its radiosensitivity. However, only a few medical facilities use gonadal shields. In addition, the contribution of internal scatter to the gonadal dose should be considered because it is unavoidable. Therefore, this study aimed to investigate the effectiveness of the gonad shield according to its thickness and to evaluate the internal scatter contribution during the rectal radiotherapy. First, a Monte Carlo simulation was performed using a simplified patient phantom that consisted of the patient's body and gonad. The dose to the gonad was assessed according to the thickness of the gonad shield, beam direction, and the distance between the gonad and irradiation field. The internal scatter contribution was calculated as the ratio of the gonadal doses with and without a shield. Second, a mesh-type reference computational phantom (MRCP) was employed to calculate the internal scatter contribution to the gonadal dose in rectal radiotherapy. Subsequently, the contribution of internal scatter was investigated by analyzing the dosimetry results in actual patient cases. The gonad shield reduced 50-75% of the gonadal dose according to its thickness from 0.5-3 cm. The internal scatter contribution ranged from 55-65% for the simplified phantom, whereas it was 75% on average for MRCP. The dosimetry results from the clinical case were similar to those of both the simplified phantom and MRCP, that is, the internal scatter contribution varied from 55-77% in most cases. These results are expected to improve the accuracy of rectal radiotherapy and benefit radiation shielding of the gonads.
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Affiliation(s)
- Hyojun Park
- Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Republic of Korea
| | - Jung-In Kim
- Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Republic of Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea
| | - Chang Heon Choi
- Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Republic of Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea
| | - Jong Min Park
- Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Republic of Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea
| | - Seonghee Kang
- Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Republic of Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea
| | - Hyeongmin Jin
- Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Republic of Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Republic of Korea
| | - Jaeman Son
- Department of Radiation Oncology, Seoul National University Hospital, Republic of Korea
- Institute of Radiation Medicine, Seoul National University Medical Research Center, Republic of Korea
- Biomedical Research Institute, Seoul National University Hospital, Republic of Korea
- Department of Radiation Oncology, Seoul National University College of Medicine, Republic of Korea
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Wilt JK, Thomson MD. "If I Start [Primary Prevention] Now, I Can Prevent [Cancer]": College Students Endorse Cancer Prevention Education. JOURNAL OF CANCER EDUCATION : THE OFFICIAL JOURNAL OF THE AMERICAN ASSOCIATION FOR CANCER EDUCATION 2025:10.1007/s13187-025-02574-6. [PMID: 39969777 DOI: 10.1007/s13187-025-02574-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/23/2025] [Indexed: 02/20/2025]
Abstract
Early onset colorectal cancer has been linked to lifestyle-related risk factors. Emerging adulthood (ages 18-25) has the greatest changes to lifestyle health behaviors with implications for health outcomes. College students have moderate consideration of future cancer risk (CFC-CA) when navigating current health behavior choices. This study explored cancer prevention knowledge, attitudes and behavioral intentions in a subset of students with low, medium and high CFC-CA. Qualitative interviews were used to explore cancer prevention among a sample of college students. We identified a stratified sample (N = 43) of high CFC-CA (n = 16), medium CFC-CA (n = 14), and low CFC-CA (n = 13) students who agreed to complete a 60-min interview on Zoom. Interviews were transcribed verbatim, and transcripts were coded using an iterative, line-by-line approach. Group comparisons were completed after coding was complete. Students exhibited greatest awareness of highly publicized cancers including the lung, breast, and skin. Fifty-four percent of those with low CFC-CA and 87% with high CFC-CA believe that their current health behavioral intentions are protective against cancer. Most students want more cancer education regardless of CFC-CA level to know how they can reduce their cancer risk. Differences in preferred information sources (indirect vs direct) were identified for low versus higher CFC-CA, respectively. Students' preferences for cancer education were related to their CFC-CA scores. This could be used to tailor information content and delivery modality. Delivering cancer prevention education through means that facilitate internal reflection may be more effective for improving risk reduction behaviors.
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Affiliation(s)
- Jacqueline Knight Wilt
- Department of Social and Behavioral Sciences, School of Public Health, Virginia Commonwealth University, One Capital Square, Box 980430, Richmond, VA, USA
| | - Maria D Thomson
- Department of Social and Behavioral Sciences, School of Public Health, Virginia Commonwealth University, One Capital Square, Box 980430, Richmond, VA, USA.
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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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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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Pallathadka H, Hsu CY, Obaid Saleh R, Renuka Jyothi S, Kumar A, Yumashev A, Sinha A, Hussein Zwamel A, Abed Jawad M, Alsaadi SB. Specific small interfering RNAs (siRNAs) for targeting the metastasis, immune responses, and drug resistance of colorectal cancer cells (CRC). Int Immunopharmacol 2024; 140:112730. [PMID: 39083927 DOI: 10.1016/j.intimp.2024.112730] [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: 06/06/2024] [Revised: 07/05/2024] [Accepted: 07/17/2024] [Indexed: 08/02/2024]
Abstract
Colorectal cancer (CRC) involves various genetic alterations, with liver metastasis posing a significant clinical challenge. Furthermore, CRC cells mostly show an increase in resistance to traditional treatments like chemotherapy. It is essential to investigate more advanced and effective therapies to prevent medication resistance and metastases and extend patient life. As a result, it is anticipated that small interfering RNAs (siRNAs) would be exceptional instruments that can control gene expression by RNA interference (RNAi). In eukaryotes, RNAi is a biological mechanism that destroys specific messenger RNA (mRNA) molecules, thereby inhibiting gene expression. In the management of CRC, this method of treatment represents a potential therapeutic agent. However, it is important to acknowledge that siRNA therapies have significant issues, such as low serum stability and nonspecific absorption into biological systems. Delivery mechanisms are thus being created to address these issues. In the current work, we address the potential benefits of siRNA therapy and outline the difficulties in treating CRCby focusing on the primary signaling pathways linked to metastasis as well as genes implicated in the multi-drug resistance (MDR) process.
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Affiliation(s)
| | - Chou-Yi Hsu
- Thunderbird School of Global Management, Arizona State University Tempe Campus, Phoenix, Arizona 85004, USA.
| | - Raed Obaid Saleh
- Department of Medical Laboratory Techniques, Al-Maarif University College, Al-Anbar, Iraq.
| | - S Renuka Jyothi
- Department of Biotechnology and Genetics, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, India.
| | - Ashwani Kumar
- Department of Pharmacy, Vivekananda Global University, Jaipur, Rajasthan 303012, India
| | - Alexey Yumashev
- Department of Prosthetic Dentistry, Sechenov First Moscow State Medical University, Russia.
| | - Aashna Sinha
- School of Applied and Life Sciences, Divison of Research and Innovation Uttaranchal University, Dehradun, Uttarakhand, India
| | - Ahmed Hussein Zwamel
- Medical Laboratory Technique College, the Islamic University, Najaf, Iraq; Medical Laboratory Technique College, the Islamic University of Al Diwaniyah, Al Diwaniyah, Iraq; Medical Laboratory Technique college, the Islamic University of Babylon, Babylon, Iraq.
| | | | - Salim B Alsaadi
- Department of Pharmaceutics, Al-Hadi University College, Baghdad 10011, Iraq.
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Wang M, Yu K, Fu W, Yang L. The combination of SHP099 inhibits the malignant biological behavior of L-OHP/5-FU-resistant colorectal cancer cells by regulating energy metabolism reprogramming. Biochem Biophys Res Commun 2024; 728:150262. [PMID: 38959530 DOI: 10.1016/j.bbrc.2024.150262] [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: 03/18/2024] [Revised: 05/31/2024] [Accepted: 06/11/2024] [Indexed: 07/05/2024]
Abstract
BACKGROUND AND OBJECTIVE Colorectal cancer (CRC) is one of the most common malignancies in China. At present, there is a problem that the CRC treatment drugs SHP099, L-OHP and 5-FU are insensitive to tumor cells. Combination medication is an important means to solve the insensitivity of medication alone. The purpose of this project was to explore the effect and molecular mechanism of SHP099 combination on the malignant biological behavior of L-OHP/5-FU resistant strains of CRC. METHODS HT29 and SW480 cells were cultured in media supplemented with L-OHP or 5-FU to establish drug-resistant strains. HT29 and SW480 drug-resistant cells were subcutaneously injected into the ventral nerves of nude mice at a dose of 5 × 106 to establish CRC drug-resistant animal models. CCK-8, Western blot, flow cytometry, Transwell and kit detection were used to detect the regulatory mechanism of energy metabolism reprogramming in drug-resistant CRC cells. RESULTS Compared with nonresistant strains, L-OHP/5-FU-resistant strains exhibited greater metabolic reprogramming. Functionally, SHP099 can restrain the metabolic reprogramming of L-OHP/5-FU-resistant strains and subsequently restrain the proliferation, colony formation, migration and spheroid formation of L-OHP/5-FU-resistant strains. Downstream mechanistic studies have shown that SHP099 interferes with the metabolic reprogramming of L-OHP/5-FU drug-resistant strains by suppressing the PI3K/AKT pathway, thereby restraining the malignant biological behavior of L-OHP/5-FU drug-resistant strains and alleviating CRC. CONCLUSION The combination of SHP099 can restrain the malignant biological behavior of L-OHP/5-FU-resistant CRC cells and alleviate the progression of CRC by interfering with the reprogramming of energy metabolism. This study explored the effect of SHP099 combination on dual-resistant CRC cells for the first time, and provided a new therapeutic idea for solving the problem of SHP099 insensitivity to CRC cells.
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Affiliation(s)
- Meilian Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China
| | - Kun Yu
- Department of Colorectal Surgery, Yunnan Cancer Hospital (The Third Affiliated Hospital of Kunming Medical University), Kunming, 650118, China
| | - Wen Fu
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China
| | - Lihong Yang
- Department of Gastroenterology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, China.
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8
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Ou WT, Tan RJ, Zhai JW, Sun LJ, Xu FP, Huang XJ, Quan ZH, Zhou CJ. Silencing GDI2 inhibits proliferation, migration and invasion of colorectal cancer through activation of p53 signaling pathway. Heliyon 2024; 10:e37770. [PMID: 39323841 PMCID: PMC11422032 DOI: 10.1016/j.heliyon.2024.e37770] [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: 04/17/2024] [Revised: 09/06/2024] [Accepted: 09/09/2024] [Indexed: 09/27/2024] Open
Abstract
Objective To investigate the effect of silencing GDP dissociation inhibitor 2 (GDI2) on colorectal cancer development and possible mechanisms based on transcriptomic analysis. Methods The differences in the expression levels of GDI2 in normal colorectal tissues and tumor tissues of colorectal cancer (CRC) patients were detected. The correlation of GDI2 expression levels with survival and clinical characteristics of CRC patients was analyzed. The effects of GDI2 expression levels on the biological functions of CRC cells were examined by CCK-8 assay, plate clone formation assay, wound healing assay, and Transwell assay. The effect of GDI2 on the proliferation and growth of xenograft tumors was investigated by a xenograft tumor model of CRC in nude mice. Based on transcriptomics, we explored the possible mechanisms and associated pathways of the effect of silencing GDI2 on CRC cells. Cellular experiments and Western blot assays were performed to verify the potential mechanisms and related pathway of GDI2 action on CRC. Results The expression levels of GDI2 in CRC tissues and cells were higher than those in normal tissues and cells. The expression level of GDI2 correlated with clinical characteristics such as lymphatic metastasis, tumor stage, tumor volume, and lymphocyte count. Silencing of GDI2 reduced the proliferative activity and migration and invasion ability of CRC cells, as well as inhibited the proliferation of CRC xenograft tumors. The differentially expressed genes were significantly enriched in biological processes such as cell cycle arrest and the p53 signaling pathway after GDI2 silencing. The percentage of G0/G1 phase cells in CRC cells was increased after silencing GDI2 as verified by flow cytometry. RAB5A was highly associated with the p53 pathway and could interact with TP53 via the ZFYVE20 protein. The mutual binding between GDI2 protein and RAB5A protein was verified by immunoprecipitation assay. Silencing GDI2 while overexpressing RAB5A reversed the reduced proliferation, migration, and invasion ability as well as cell cycle arrest of CRC cells. Meanwhile, the addition of p53 signaling pathway inhibitor Pifithrin-α (PFT-α) also reversed the biological effects of silencing GDI2 on CRC cells. The p-p21 and p-p53 protein expression levels were significantly greater in the sh-GDI2 group than in the sh-NC group. However, the p-p21 and p-p53 protein expression levels were reduced after silencing GDI2 while overexpressing RAB5A. Conclusion Silencing GDI2 activates the p53 signaling pathway by regulating RAB5A expression levels, which in turn induces cell cycle arrest and ultimately affects the proliferative activity, migration, and invasive ability of CRC cells.
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Affiliation(s)
- Wen-Ting Ou
- Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, 524001, China
| | - Rong-Jian Tan
- Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, 524001, China
| | - Jia-Wei Zhai
- Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, 524001, China
| | - Li-Jun Sun
- Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, 524001, China
| | - Fei-Peng Xu
- Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, 524001, China
| | - Xian-Jin Huang
- Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, 524001, China
| | - Zhen-Hao Quan
- Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, 524001, China
| | - Cai-Jin Zhou
- Affiliated Hospital of Guangdong Medical University, No. 57, South of Renmin Avenue, Zhanjiang, 524001, China
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9
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Mąkosza KM, Muc-Wierzgoń M, Dzięgielewska-Gęsiak S. Nutrition and Selected Lifestyle Elements as a Tertiary Prevention in Colorectal Cancer Patients. Nutrients 2024; 16:3129. [PMID: 39339729 PMCID: PMC11435162 DOI: 10.3390/nu16183129] [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: 08/13/2024] [Revised: 09/11/2024] [Accepted: 09/15/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Nutrition and lifestyle elements can significantly support the therapeutic process in colorectal cancer (CRC) patients, which is the basis for tertiary prevention. The study aimed to assess the nutritional strategies and lifestyle of CRC patients and to determine differences in these behaviors depending on gender and age. METHODS The study group included 202 CRC patients. The research was carried out in two hospitals and using the snowball method. The research tool was an original questionnaire. Data were processed in statistical programs. p < 0.05 was considered statistically significant. RESULTS Patients reported many behavioral-nutritional side effects. Half of them did not use a therapeutic diet (n = 101; 50.0%). The majority of patients declared that they ate three meals a day (57.4%). Fruits and vegetables were mainly eaten raw (69.3%). Almost a quarter of patients were not physically active at all (22.3%). Men chose to fry meat significantly more often than women (27.7% vs. 19.3%) (p = 0.003). The elderly consumed fast food significantly less often than middle-aged (88.5% vs. 72.3%) (p = 0.03). CONCLUSIONS Patients showed both pro- and anti-health activities. The findings revealed several noteworthy disparities in dietary habits and lifestyle choices based on gender and age, indicating that these factors can significantly influence the health management of CRC patients. The patients' behaviors should be constantly monitored and intensified, especially through regular consultations and educational meetings with an oncology dietitian for nutritional tertiary prevention of chronic disease.
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Affiliation(s)
- Kamil Michał Mąkosza
- Doctoral School, Medical University of Silesia, 40-055 Katowice, Poland
- Department of Internal Diseases Propaedeutics and Emergency Medicine, Faculty of Public Health in Bytom, Medical University of Silesia, 40-055 Katowice, Poland
| | - Małgorzata Muc-Wierzgoń
- Department of Internal Diseases Propaedeutics and Emergency Medicine, Faculty of Public Health in Bytom, Medical University of Silesia, 40-055 Katowice, Poland
| | - Sylwia Dzięgielewska-Gęsiak
- Department of Internal Diseases Propaedeutics and Emergency Medicine, Faculty of Public Health in Bytom, Medical University of Silesia, 40-055 Katowice, Poland
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10
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Suresh RS, Garcia LE, Gearhart SL. Young-Onset Rectal Cancer: Is It for Real? Adv Surg 2024; 58:275-291. [PMID: 39089782 DOI: 10.1016/j.yasu.2024.04.015] [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] [Indexed: 08/04/2024]
Abstract
The incidence of early-onset colorectal cancer has been rising over the last two decades. Tumors in young patients have distinct features compared to older patients. They predominantly arise in the distal colon and rectum and have poor histological features. Patients tend to present at a more advanced stage and be exposed to more aggressive management approaches; however, this has not translated into a significant survival benefit compared to their older counterparts. This chapter will share current evidence on risk factors and management options for early onset colorectal cancer with a focus on rectal cancer.
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Affiliation(s)
- Reena S Suresh
- Department of Surgery, Division of Colorectal Surgery, Johns Hopkins School of Medicine, 600 N. Wolfe Street / Blalock 618, Baltimore, MD 21287, USA
| | - Leonardo E Garcia
- Department of Surgery, Division of Colorectal Surgery, Johns Hopkins School of Medicine, 600 N. Wolfe Street / Blalock 618, Baltimore, MD 21287, USA
| | - Susan L Gearhart
- Department of Surgery, Division of Colorectal Surgery, Johns Hopkins School of Medicine, 600 N. Wolfe Street / Blalock 618, Baltimore, MD 21287, USA.
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11
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Siromoni B, Groman A, Parmar K, Mukherjee S, Vadehra D. Exploring Demographic Differences and Outcomes in Early-Onset Colorectal Cancer. JCO Oncol Pract 2024; 20:1075-1080. [PMID: 38394477 DOI: 10.1200/op.23.00671] [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: 10/17/2023] [Revised: 12/17/2023] [Accepted: 01/16/2024] [Indexed: 02/25/2024] Open
Abstract
PURPOSE Early-onset colorectal cancer (EOCRC), defined as CRC diagnosed before age 50 years, has increased significantly worldwide. The majority of EOCRCs do not appear to be driven by genetic factors and may be influenced by environmental factors. We hypothesized that sociodemographic disparities exist in EOCRC. The purpose was of the study was to examine the geographic disparities in patients with EOCRC. METHODS We retrospectively examined the SEER database from 1976 to 2016 to examine the geographic disparities in EOCRC. A total of 73,378 patients with EOCRC were included in the analysis. We performed univariate and multivariable analyses to evaluate overall survival (OS) and disease-specific survival (DSS). Sociodemographic factors, including the location of residence (metropolitan areas [MA] or rural areas [RA]), sex, race, insurance status, and marital status, were included in the statistical analysis. RESULTS The incidence and mortality rates were consistently higher in RA versus MA during the study period. Multivariable analysis showed that patients living in RA had worse OS (hazard ratio [HR], 1.14; P < .01) and DSS (HR, 1.15; P < .001) compared with those living in MA. Similarly, non-Hispanic Black ethnicity and uninsured patients had significantly worse survival when compared with non-Hispanic White and insured patients, respectively. Married status showed better survival outcomes. CONCLUSION Patients with EOCRC living in RA have worse outcomes. Understanding the mechanisms behind such socioeconomic disparities is important so that future studies can reduce these disparities.
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Affiliation(s)
| | | | - Kanak Parmar
- Texas Tech University Health Sciences Center, Lubbock, TX
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12
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Jafari A, Hosseini FA, Jalali FS. A systematic review of the economic burden of colorectal cancer. Health Sci Rep 2024; 7:e70002. [PMID: 39170890 PMCID: PMC11336656 DOI: 10.1002/hsr2.70002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2023] [Revised: 04/08/2024] [Accepted: 08/01/2024] [Indexed: 08/23/2024] Open
Abstract
Background Colorectal cancer is the third most common cancer in the Western Hemisphere. It is the third most common cancer in men after prostate and lung cancers and the second most common cancer in women after breast cancer. According to some studies, the incidence and prevalence of colorectal cancer is increasing rapidly. Main Body In the present study, a systematic review of the articles related to the economic burden of colorectal cancer was carried out. The articles were taken from the following databases: SID, Medline/Pubmed, Embase, Scopus, Web of Science, NHS Economic Evaluation Database (EED), Econlit, and Google Scholar. Furthermore, the PICOTS model was used to select the inclusion criteria. The quality of the articles' methodologies was evaluated using Drummond's checklist. Then, some data were extracted from relevant articles, in terms of year, place of research, sample size, costing approach, type of measured costs, average direct medical costs, average direct nonmedical costs, and average indirect costs. The data from 37 studies dealing with the costs of patients with colorectal cancer were extracted. Most of the studies were conducted in the United States, and the social perspective was the most common perspective to measure the costs. According to the majority of the studies, direct medical costs were considered the greatest driver in causing the economic burden of colorectal cancer. The costs of hospitalization, medicine, surgery, chemotherapy, and radiotherapy accounted for the largest share of direct medical costs, and the costs of transportation, accommodation, and home care were the greatest share of direct nonmedical costs. Furthermore, the costs associated with disability, absenteeism, and premature death were identified as the main drivers of indirect costs. Conclusion The findings of this study showed that colorectal cancer imposes great direct and indirect costs on families, the health system, and society. The best way to deal with this disease and, hence, to reduce its economic burden is to take comprehensive preventive measures and modify the lifestyle. In addition, health policymakers can limit the costs of this disease by expanding the screening program.
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Affiliation(s)
- Abdosaleh Jafari
- School of Health Management and Information Sciences, Health Human Resources Research CenterShiraz University of Medical SciencesShirazIran
| | | | - Faride S. Jalali
- School of Health Management and Information Sciences, Health Human Resources Research CenterShiraz University of Medical SciencesShirazIran
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13
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Yan H, Ou Q, Chang Y, Liu J, Chen L, Guo D, Zhang S. 5-Fluorouracil resistance-based immune-related gene signature for COAD prognosis. Heliyon 2024; 10:e34535. [PMID: 39130472 PMCID: PMC11315090 DOI: 10.1016/j.heliyon.2024.e34535] [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: 02/21/2024] [Revised: 06/29/2024] [Accepted: 07/11/2024] [Indexed: 08/13/2024] Open
Abstract
Background Drug resistance is the primary obstacle to advanced tumor therapy and the key risk factor for tumor recurrence and death. 5-Fluorouracil (5-FU) chemotherapy is the most common chemotherapy for individuals with colorectal cancer, despite numerous options. Methods The Gene Expression Omnibus database was utilized to extract expression profile data of HCT-8 human colorectal cancer wild-type cells and their 5-FU-induced drug resistance cell line. These data were used to identify 5-FU resistance-related differentially expressed genes (5FRRDEGs), which intersected with the colorectal adenocarcinoma (COAD) transcriptome data provided by the Cancer Genome Atlas Program database. A prognostic signature containing five 5FRRDEGs (GOLGA8A, KLC3, TIGD1, NBPF1, and SERPINE1) was established after conducting a Cox regression analysis. We conducted nomogram development, drug sensitivity analysis, tumor immune microenvironment analysis, and mutation analysis to assess the therapeutic value of the prognostic qualities. Results We identified 166 5FRRDEGs in patients with COAD. Subsequently, we created a prognostic model consisting of five 5FRRDEGs using Cox regression analysis. The patients with COAD were divided into different risk groups by risk score; the high-risk group demonstrated a worse prognosis than the low-risk group. Conclusion In summary, the 5FRRDEG-based prognostic model is an effective tool for targeted therapy and chemotherapy in patients with COAD. It can accurately predict the survival prognosis of these patients as well as to provide the direction for exploring the resistance mechanism underlying COAD.
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Affiliation(s)
- Haixia Yan
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
| | - Qinling Ou
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
| | - Yonglong Chang
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
| | - Jinhui Liu
- College of Integrated Traditional Chinese & Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, 410208, China
| | - Linzi Chen
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
| | - Duanyang Guo
- College of Integrated Traditional Chinese & Western Medicine, Hunan University of Traditional Chinese Medicine, Changsha, Hunan, 410208, China
| | - Sifang Zhang
- Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China
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14
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Meyer NH, Kotnik N, Noubissi Nzeteu GA, van Kempen LC, Mastik M, Bockhorn M, Troja A. Unraveling the MicroRNA tapestry: exploring the molecular dynamics of locoregional recurrent rectal cancer. Front Oncol 2024; 14:1407217. [PMID: 39070144 PMCID: PMC11272531 DOI: 10.3389/fonc.2024.1407217] [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: 03/26/2024] [Accepted: 06/21/2024] [Indexed: 07/30/2024] Open
Abstract
Introduction Colorectal cancer (CRC) ranks as the third most prevalent malignancy globally, with a concerning rise in incidence among young adults. Despite progress in understanding genetic predispositions and lifestyle risk factors, the intricate molecular mechanisms of CRC demand exploration. MicroRNAs (miRNAs) emerge as key regulators of gene expression and their deregulation in tumor cells play pivotal roles in cancer progression. Methods NanoString's nCounter technology was utilized to measure the expression of 827 cancer-related miRNAs in tumor tissue and adjacent non-involved normal colon tissue from five patients with locoregional CRC progression. These expression profiles were then compared to those from the primary colon adenocarcinoma (COAD) cohort in The Cancer Genome Atlas (TCGA). Results and discussion Intriguingly, 156 miRNAs showed a contrasting dysregulation pattern in reccurent tumor compared to their expression in the TCGA COAD cohort. This observation implies dynamic alterations in miRNA expression patterns throughout disease progression. Our exploratory study contributes to understanding the regulatory landscape of recurrent CRC, emphasizing the role of miRNAs in disease relapse. Notable findings include the prominence of let-7 miRNA family, dysregulation of key target genes, and dynamic changes in miRNA expression patterns during progression. Univariate Cox proportional hazard models highlighted miRNAs associated with adverse outcomes and potential protective factors. The study underscores the need for more extensive investigations into miRNA dynamics during tumor progression and the value of stage specific biomarkers for prognosis.
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Affiliation(s)
- N. Helge Meyer
- Department of Human Medicine, School of Medicine and Health Sciences, Klinikum Oldenburg, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, Germany
| | - Nika Kotnik
- Department of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg, Oldenburg, Germany
- Center for Blistering Diseases, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Gaetan Aime Noubissi Nzeteu
- Department of Human Medicine, School of Medicine and Health Sciences, Klinikum Oldenburg, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, Germany
| | - Léon C. van Kempen
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
- Department of Pathology, Antwerp University Hospital, University of Antwerp, Antwerp, Belgium
| | - Mirjam Mastik
- Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands
| | - Maximilian Bockhorn
- Department of Human Medicine, School of Medicine and Health Sciences, Klinikum Oldenburg, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, Germany
| | - Achim Troja
- Department of Human Medicine, School of Medicine and Health Sciences, Klinikum Oldenburg, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, Germany
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15
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Wang Y, Wu ZL, Wang YG, Wang H, Jia XY. Early colorectal cancer screening–no time to lose. World J Gastroenterol 2024; 30:2959-2963. [PMID: 38946873 PMCID: PMC11212702 DOI: 10.3748/wjg.v30.i23.2959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2024] [Revised: 05/15/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
In this editorial, we comment on the article entitled “Stage at diagnosis of colorectal cancer through diagnostic route: Who should be screened?” by Agatsuma et al. Colorectal cancer (CRC) is emerging as an important health issue as its incidence continues to rise globally, adversely affecting the quality of life. Although the public has become more aware of CRC prevention, most patients lack screening awareness. Some poor lifestyle practices can lead to CRC and symptoms can appear in the early stages of CRC. However, due to the lack of awareness of the disease, most of the CRC patients are diagnosed already at an advanced stage and have a poor prognosis.
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Affiliation(s)
- Ying Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou 310018, Zhejiang Province, China
| | - Zheng-Long Wu
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Yi-Gang Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
| | - Hui Wang
- Department of Oncology, Zhejiang Xiaoshan Hospital, Hangzhou 310018, Zhejiang Province, China
| | - Xiao-Yuan Jia
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, Zhejiang Province, China
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16
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Savu E, Șurlin V, Vasile L, Petrescu IO, Singer CE, Pirici ND, Mogoanta SS. Early-Onset Colorectal Cancer-A Retrospective Study from a Tertiary Referral Hospital in Romania. Diagnostics (Basel) 2024; 14:1052. [PMID: 38786350 PMCID: PMC11119205 DOI: 10.3390/diagnostics14101052] [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: 03/24/2024] [Revised: 05/02/2024] [Accepted: 05/17/2024] [Indexed: 05/25/2024] Open
Abstract
Early-onset colorectal cancer emerges as a distinctive clinical and biological entity and is generally defined as the onset of colon or rectal neoplasia before the age of 50. Several reports describe an increasing incidence worldwide of colorectal cancers occurring in individuals younger than 50 years, along with particular histologic and molecular features. Although heredity may be an explanation in some cases with young-onset colorectal cancer, other driving factors remain partially unknown. The present study explores demographic, clinical, and pathological features within a group of patients diagnosed with colorectal cancer before the age of 50. It is a retrospective survey based on data collected between 2017 and 2023 within three surgical departments from a tertiary Romanian hospital. The clinical and pathological features we identified (later-stage disease, distal colon tumor localization, mucinous histology) are mainly superimposed with the existing data in the literature regarding this pathology. In order to lower the burden that colorectal neoplasia diagnosed in the young implies, a change of paradigm should be made in terms of establishing effective and targeted screening programs but also in the direction of enhancing complex clinical, pathological, and molecular diagnosis.
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Affiliation(s)
- Elena Savu
- Doctoral School, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
- Department of Oncopediatrics, Clinical Emergency County Hospital, 200642 Craiova, Romania
| | - Valeriu Șurlin
- Department of General Surgery, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
- First General Surgery Department, Clinical Emergency County Hospital, 200642 Craiova, Romania
| | - Liviu Vasile
- Department of Surgical Semiology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
- Third General Surgery Department, Clinical Emergency County Hospital, 200642 Craiova, Romania;
| | - Ileana Octavia Petrescu
- Department of Pediatrics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (I.O.P.); (C.E.S.)
- Second Pediatrics Department, Clinical Emergency County Hospital, 200642 Craiova, Romania
| | - Cristina Elena Singer
- Department of Pediatrics, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania; (I.O.P.); (C.E.S.)
- Second Pediatrics Department, Clinical Emergency County Hospital, 200642 Craiova, Romania
| | - Nicolae-Daniel Pirici
- Department of Histology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Stelian Stefanita Mogoanta
- Third General Surgery Department, Clinical Emergency County Hospital, 200642 Craiova, Romania;
- Department of General Surgery, Faculty of Dental Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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17
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Liu Y, Wang Y, Yu Z, Wang Z. Impacts of TP53TG1 in cancer-associated fibroblasts-derived exosomes on epithelial-mesenchymal transition capacity of colorectal carcinoma cells by targeting miR-330-3p. Heliyon 2024; 10:e30301. [PMID: 38707274 PMCID: PMC11068805 DOI: 10.1016/j.heliyon.2024.e30301] [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: 01/29/2024] [Revised: 04/21/2024] [Accepted: 04/23/2024] [Indexed: 05/07/2024] Open
Abstract
Objective This research aims at clarifying the action and mechanisms of action of TP53TG1 in cancer-associated fibroblasts (CAF)-derived exosomes (EXs) on colorectal carcinoma (CRC) cells. Methods CAF and CAF-EXs isolated from CRC tissues were incubated with CRC SW480 cells to determine alterations in biological behavior, epithelial-mesenchymal transition (EMT) capacity, and TP53TG1 and miR-330-3p expression. In addition, a dual luciferase reporter (DLR) assay was conducted to verify the connection between TP53TG1 and miR-330-3p, and the impacts of the two genes on CRC cells were analyzed. Results CRC-CAF-EXs extracted from CRC tissues were successfully identified and were able to promote SW480 multiplication, invasiveness, migration, and EMT ability while inhibiting apoptosis (P < 0.05). In addition, TP53TG1 increased and miR-330-3p decreased in SW480 when cultured with CRC-CAF-EXs (P < 0.05). The DLR assay identified notably reduced fluorescence activity of TP53TG1-WT after transfection with miR-330-3p-mimics (P < 0.05). Furthermore, SW480 cell multiplication, invasiveness and migration were found to be enhanced and the apoptosis decreased after up-regulating TP53TG1, while suppressing TP53TG1 and up-regulating miR-330-3p contributed to quite the opposite effect (P < 0.05). Moreover, by elevating TP53TG1 and miR-330-3p simultaneously, we found a cell activity similar to the NC group (P > 0.05). Conclusion By targeting miR-330-3p, TP53TG1 in CRC-CAF-EXs can enhance CRC cell activity and EMT capacity and inhibit apoptosis.
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Affiliation(s)
- Yawei Liu
- Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, China
| | - Youwei Wang
- Bengbu Medical College, Bengbu, Anhui, 233030, China
| | - Zhijuan Yu
- Hubei University of Science and Technology, Xianning, Hubei, 437000, China
| | - Ziheng Wang
- Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Taipa, Macao SAR, China
- Suzhou Industrial Park Monash Research Institute of Science and Technology, Suzhou, Jiangsu, 215000, China
- The School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
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Demb J, Kolb JM, Dounel J, Fritz CDL, Advani SM, Cao Y, Coppernoll-Blach P, Dwyer AJ, Perea J, Heskett KM, Holowatyj AN, Lieu CH, Singh S, Spaander MCW, Vuik FER, Gupta S. Red Flag Signs and Symptoms for Patients With Early-Onset Colorectal Cancer: A Systematic Review and Meta-Analysis. JAMA Netw Open 2024; 7:e2413157. [PMID: 38787555 PMCID: PMC11127127 DOI: 10.1001/jamanetworkopen.2024.13157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 03/19/2024] [Indexed: 05/25/2024] Open
Abstract
IMPORTANCE Early-onset colorectal cancer (EOCRC), defined as a diagnosis at younger than age 50 years, is increasing, and so-called red flag signs and symptoms among these individuals are often missed, leading to diagnostic delays. Improved recognition of presenting signs and symptoms associated with EOCRC could facilitate more timely diagnosis and impact clinical outcomes. OBJECTIVE To report the frequency of presenting red flag signs and symptoms among individuals with EOCRC, to examine their association with EOCRC risk, and to measure variation in time to diagnosis from sign or symptom presentation. DATA SOURCES PubMed/MEDLINE, Embase, CINAHL, and Web of Science were searched from database inception through May 2023. STUDY SELECTION Studies that reported on sign and symptom presentation or time from sign and symptom presentation to diagnosis for patients younger than age 50 years diagnosed with nonhereditary CRC were included. DATA EXTRACTION AND SYNTHESIS Data extraction and quality assessment were performed independently in duplicate for all included studies using Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guidelines. Joanna Briggs Institute Critical Appraisal tools were used to measure risk of bias. Data on frequency of signs and symptoms were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES Outcomes of interest were pooled proportions of signs and symptoms in patients with EOCRC, estimates for association of signs and symptoms with EOCRC risk, and time from sign or symptom presentation to EOCRC diagnosis. RESULTS Of the 12 859 unique articles initially retrieved, 81 studies with 24 908 126 patients younger than 50 years were included. The most common presenting signs and symptoms, reported by 78 included studies, were hematochezia (pooled prevalence, 45% [95% CI, 40%-50%]), abdominal pain (pooled prevalence, 40% [95% CI, 35%-45%]), and altered bowel habits (pooled prevalence, 27% [95% CI, 22%-33%]). Hematochezia (estimate range, 5.2-54.0), abdominal pain (estimate range, 1.3-6.0), and anemia (estimate range, 2.1-10.8) were associated with higher EOCRC likelihood. Time from signs and symptoms presentation to EOCRC diagnosis was a mean (range) of 6.4 (1.8-13.7) months (23 studies) and a median (range) of 4 (2.0-8.7) months (16 studies). CONCLUSIONS AND RELEVANCE In this systematic review and meta-analysis of patients with EOCRC, nearly half of individuals presented with hematochezia and abdominal pain and one-quarter with altered bowel habits. Hematochezia was associated with at least 5-fold increased EOCRC risk. Delays in diagnosis of 4 to 6 months were common. These findings highlight the need to identify concerning EOCRC signs and symptoms and complete timely diagnostic workup, particularly for individuals without an alternative diagnosis or sign or symptom resolution.
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Affiliation(s)
- Joshua Demb
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Jennifer M. Kolb
- Vatche and Tamar Manoukian Division of Digestive Diseases, David Geffen School of Medicine at UCLA, VA Greater Los Angeles Healthcare System, Los Angeles, California
| | - Jonathan Dounel
- Department of Medicine, University of California San Diego, La Jolla
| | | | - Shailesh M. Advani
- Department of Internal Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York
| | - Yin Cao
- Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, St Louis, Missouri
- Division of Gastroenterology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri
- Alvin J. Siteman Cancer Center, Washington University School of Medicine, St Louis, Missouri
| | | | - Andrea J. Dwyer
- University of Colorado Cancer Center, Colorado School of Public Health, Aurora
| | - Jose Perea
- Molecular Medicine Unit, Department of Medicine, Biomedical Research Institute of Salamanca, University of Salamanca, Salamanca, Spain
- Surgery Department, Vithas Arturo Soria University Hospital, Madrid, Spain
| | - Karen M. Heskett
- UC San Diego Library, University of California San Diego, La Jolla
| | - Andreana N. Holowatyj
- Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Vanderbilt University School of Medicine, Nashville, Tennessee
| | - Christopher H. Lieu
- Division of Medical Oncology, University of Colorado Denver Anschutz Medical Campus, Aurora
| | - Siddharth Singh
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Manon C. W. Spaander
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Fanny E. R. Vuik
- Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Samir Gupta
- Division of Gastroenterology, Department of Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
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Popescu I, Dudău AM, Dima S, Herlea V, Croitoru VM, Dinu IM, Miron M, Lupescu I, Croitoru-Cazacu IM, Dumitru R, Croitoru AE. Multimodal Treatment of Metastatic Rectal Cancer in a Young Patient: Case Report and Literature Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:696. [PMID: 38792879 PMCID: PMC11123219 DOI: 10.3390/medicina60050696] [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: 03/03/2024] [Revised: 04/14/2024] [Accepted: 04/19/2024] [Indexed: 05/26/2024]
Abstract
Metastatic colorectal cancer requires a multidisciplinary and individualized approach. Herein, we reported the case of a young woman diagnosed with metastatic rectal cancer who received an individualized multimodal treatment strategy that resulted in a remarkable survival. There were several particular aspects of this case, such as the early onset of the disease, the successful use of conversion therapy, the application of liquid biopsy to guide treatment, and the specific nature of the bone metastasis. To offer more insights for navigating such challenges in patients with metastatic colorectal cancer, we have conducted a literature review to find more data related to the particularities of this case. The incidence of early onset colorectal cancer is on the rise. Data suggests that it differs from older-onset colorectal cancer in terms of its pathological, epidemiological, anatomical, metabolic, and biological characteristics. Conversion therapy and surgical intervention provide an opportunity for cure and improve outcomes in metastatic colorectal cancer. It is important to approach each case individually, as every patient with limited liver disease should be considered as a candidate for secondary resection. Moreover, liquid biopsy has an important role in the individualized management of metastatic colorectal cancer patients, as it offers additional information for treatment decisions.
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Affiliation(s)
- Ionuț Popescu
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
| | - Ana-Maria Dudău
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Simona Dima
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Vlad Herlea
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Pathology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Vlad M. Croitoru
- Faculty of Medicine, Titu Maiorescu University, 040441 Bucharest, Romania; (I.P.); (V.M.C.)
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Ioana Mihaela Dinu
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Monica Miron
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
| | - Ioana Lupescu
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Radiology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Irina M. Croitoru-Cazacu
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
| | - Radu Dumitru
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
- Radiology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Adina Emilia Croitoru
- Medical Oncology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania; (I.M.D.); (M.M.); (I.M.C.-C.); (A.E.C.)
- Faculty of Medicine, University of Medicine and Pharmacy Carol Davila, 020021 Bucharest, Romania; (S.D.); (V.H.); (I.L.); (R.D.)
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Atchade AM, Williams JL, Mermelstein L, Nemesure B. Unraveling the complexities of early-onset colorectal cancer: a perspective on dietary and microbial influences. Front Public Health 2024; 12:1370108. [PMID: 38638485 PMCID: PMC11024228 DOI: 10.3389/fpubh.2024.1370108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 03/19/2024] [Indexed: 04/20/2024] Open
Abstract
While advances in screening have resulted in declining rates of colorectal cancer (CRC) among adults ≥50 years of age since the mid-2000s, the incidence of early-onset CRC (EOCRC) has steadily increased over the last decade. This increase is not fully accounted for by hereditary factors, and the hypothesis that a sedentary lifestyle and obesity are the primary culprits is not fully supported by recent reports indicating that many affected individuals lead active lifestyles, maintain normal weight, and are otherwise healthy. Attention has shifted toward dietary patterns, notably the consumption of processed and ultra-processed foods found in Western diets, which are suspected of disrupting the gut microbiome balance that potentially leads to EOCRC. The impact of antibiotic use on the gut microbiome is also posited as a contributing factor, given its rising prevalence in medical and agricultural practices. We propose that a paradigm shift is necessary for EOCRC research, moving beyond metabolic factors to a broader exploration of dietary and microbial influences. Future research must prioritize understanding the relationship between dietary habits, particularly processed food intake, antibiotic exposure, and gut microbiome dynamics, to unravel the complex etiology of EOCRC. This will be crucial in developing comprehensive preventive strategies to address the increasing incidence of this malignancy in younger populations.
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Affiliation(s)
| | | | | | - Barbara Nemesure
- Stony Brook Medicine, Stony Brook, NY, United States
- Cancer Center, Stony Brook Medicine, Stony Brook, NY, United States
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21
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Chi Y, Yuan H, Fan Q, Wang Z, Niu Z, Yu J, Yuan D. Clinical-Molecular characteristics and Post-Translational modifications of colorectal cancer in north China: Implications for future targeted therapies. Gene 2024; 899:148134. [PMID: 38185290 DOI: 10.1016/j.gene.2024.148134] [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: 09/11/2023] [Revised: 12/12/2023] [Accepted: 01/02/2024] [Indexed: 01/09/2024]
Abstract
This study delineated the elucidate molecular changes and their post-translational modifications (PTMs) in heterogenetic colorectal cancer (CRC) for a deeper understanding of the CRC pathophysiology and identifying potential therapeutic targets. In this retrospective study, the profiles of 13 hot spot gene mutations were analyzed and the microsatellite instability (MSI) status was determined.Employing the Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) assay, the clinical-pathological features of CRC were characterized in 249 Chinese patients. PTMs were quantified online.Among the patients with CRC, the mutation frequencies of KRAS, NRAS, BRAF, PIK3CA, TP53, and APC genes were 47.8%, 3.6%, 4.8%, 13.7%, 55.8%, and 36.9%, respectively. The proportion of MSI-high (MSI-H) was 7.8%.Subsequent multiple logistic regression analysis showed significant associations including a link between lung metastasis and KRAS mutation, between liver metastasis and lymph node metastasis, between MSI-H and early-onset CRC (EOCRC) and KRAS mutation, between right-sided colon cancer and peritoneal metastasis, and between PIK3CA mutation and PTEN mutation. Patients with KRAS mutation presented with MSI-H, lung metastasis, and PIK3CA mutation. MSI-H, BRAF mutation, and PTEN mutation were more frequent in EOCRC. Phosphorylation and ubiquitylation were found in KRAS, BRAF, PTEN, and SMAD4; SUMOylation and ubiquitylation were observed in HRAS and NRAS; while phosphorylation was obvious in APC, P53, and MLH1. Notably, Phosphorylation and ubiquitylation were the two most common PTMs. The biological characteristics of CRC in Chinese patients have some unique clinical features, which can be explained by the genetic mutation profile, correlations among gene mutations and clinical characteristics. These distinctions set the Chinese patient population apart from their Western counterparts.
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Affiliation(s)
- Yajing Chi
- School of Medicine, Nankai University, Tianjin, China; Cancer Center, The General Hospital of the People's Liberation Army, Beijing, China
| | - Hongtu Yuan
- Department of Pathology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Qing Fan
- Department of Pharmacy, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Zhendan Wang
- Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Zuoxing Niu
- Department of Gastroenterology Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Jinming Yu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Dandan Yuan
- Department of Gastroenterology Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China.
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22
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Long X, Wang Y, Jian ZQ, He Q. Comparison of clinical features and prognosis of early- and late-onset colorectal cancer. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2024; 32:116-122. [DOI: 10.11569/wcjd.v32.i2.116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/26/2024]
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23
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Briggs NL, Ton M, Malen RC, Reedy AM, Cohen SA, Phipps AI, Burnett-Hartman AN, Newcomb PA. Colorectal cancer pre-diagnostic symptoms are associated with anatomic cancer site. BMC Gastroenterol 2024; 24:65. [PMID: 38317073 PMCID: PMC10845784 DOI: 10.1186/s12876-024-03152-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2023] [Accepted: 01/29/2024] [Indexed: 02/07/2024] Open
Abstract
BACKGROUND Signs and red flag symptoms in colorectal cancer (CRC) patients who are below the recommended screening age are often overlooked, leading to delayed diagnosis and worse prognosis. This study investigates how patient pre-diagnostic symptoms are associated with anatomic site of their cancer and whether the association varies by age at CRC diagnosis. METHODS We ascertained CRC patients' experienced symptoms and screening through medical abstractions from an ongoing population-based study of CRC patients identified through a SEER cancer registry (N = 626). We used logistic regression to estimate odds ratios and 95% confidence intervals for the association between symptoms and CRC anatomic site. Additional analyses were stratified by age at diagnosis. Early-onset was defined as less than 50 years of age at CRC diagnosis. RESULTS Participants who experienced blood in stool were more likely (odds ratio (95% confidence interval)) to have rectal (vs. colon) cancer (4.37 (3.02, 6.33)), as were patients who experienced changes to stool (1.78 (1.21, 2.60)). Patients diagnosed with colon cancer were more likely to present with abdominal pain (0.30 (0.19, 0.47)), anemia (0.40 (0.21, 0.75)), other symptoms (0.33 (0.19, 0.55)) and no symptoms (0.68 (0.44, 1.04)). When stratifying by age at diagnosis, we found that the association between blood in stool and rectal tumor location was particularly pronounced for patients with early-onset CRC (6.48 (2.73, 15.41)). CONCLUSIONS Common pre-diagnostic red flag symptoms are associated with CRC anatomic site. These findings can inform best practices for gastroenterologist triage of care and early evaluation of CRC and are of key importance given the rise of early-onset (pre-screening age) CRC. TRIAL REGISTRATION Not applicable to this study and analysis.
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Affiliation(s)
- Nicole L Briggs
- Department of Epidemiology, University of Washington School of Public Health, UW Box #351619, 3980 15th Ave NE, Seattle, WA, 98195, USA.
- Public Health Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA.
| | - Mimi Ton
- Department of Epidemiology, University of Washington School of Public Health, UW Box #351619, 3980 15th Ave NE, Seattle, WA, 98195, USA
- Public Health Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA
| | - Rachel C Malen
- Public Health Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA
| | - Adriana M Reedy
- Public Health Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA
| | - Stacey A Cohen
- Division of Oncology, University of Washington, 825 Eastlake Ave E, Seattle, WA, 98109, USA
- Clinical Research Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA
| | - Amanda I Phipps
- Department of Epidemiology, University of Washington School of Public Health, UW Box #351619, 3980 15th Ave NE, Seattle, WA, 98195, USA
- Public Health Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA
| | - Andrea N Burnett-Hartman
- Department of Epidemiology, University of Washington School of Public Health, UW Box #351619, 3980 15th Ave NE, Seattle, WA, 98195, USA
- Institute for Health Research, Kaiser Permanente, 2550 S Parker Rd, Aurora, CO, 80014, USA
| | - Polly A Newcomb
- Department of Epidemiology, University of Washington School of Public Health, UW Box #351619, 3980 15th Ave NE, Seattle, WA, 98195, USA
- Public Health Sciences Division, Fred Hutchinson Cancer Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA
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24
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Beauharnais CC, Crawford A, Springer JE, Sturrock PR, Davids JS, Maykel JA, Alavi K. Racial disparities in survival of early onset colon cancer (Age<50): A matched NCDB analysis. Am J Surg 2024; 228:141-145. [PMID: 37718168 DOI: 10.1016/j.amjsurg.2023.08.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2023] [Revised: 08/14/2023] [Accepted: 08/25/2023] [Indexed: 09/19/2023]
Abstract
BACKGROUND Early-onset colon cancer (EOCC) has increasing incidence and disproportionately affects African-Americans. This analysis aims to compare EOCC survival among Black and White patients after matching relevant socio-demographic factors and stage. METHODS The 2004-2017 NCDB database was queried for Black and White patients, age<50, who underwent colectomy for adenocarcinoma. A one-to-one match on race was performed based on sociodemographic factors and disease stage (I-IV). Five-year survival differences were analyzed with Cox proportional hazards models. RESULTS 5322 Black-White matched pairs were analyzed. Compared to White patients, Black patients averaged more days to surgery (19 ± 68 vs 16 days ± 32, p < 0.001) and to chemotherapy (63 ± 8 vs. 57 ± 39, p < 0.001). Black stage III patients were 20% less likely to receive chemotherapy (OR 0.8, 95% CI 0.7-0.9, p = 0.0006), and had a 17% increased rate of death (HR 1.17, 95% CI 1.0-1.3, p = 0.01) after adjusting for sex, comorbidity score, tumor location and chemotherapy. CONCLUSIONS Black patients with stage 3 EOCC are less likely to receive chemotherapy and have worse survival. Further evaluation is warranted to identify potential factors driving these observed.
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Affiliation(s)
- Catherine C Beauharnais
- Department of Surgery, Division of Colorectal Surgery, UMASS Memorial Health, Worcester, MA, USA; UMASS Chan Medical School, United States.
| | | | - Jeremy E Springer
- Department of Surgery, Division of Colorectal Surgery, UMASS Memorial Health, Worcester, MA, USA; UMASS Chan Medical School, United States
| | - Paul R Sturrock
- Department of Surgery, Division of Colorectal Surgery, UMASS Memorial Health, Worcester, MA, USA; UMASS Chan Medical School, United States
| | - Jennifer S Davids
- Department of Surgery, Division of Colorectal Surgery, UMASS Memorial Health, Worcester, MA, USA; UMASS Chan Medical School, United States
| | - Justin A Maykel
- Department of Surgery, Division of Colorectal Surgery, UMASS Memorial Health, Worcester, MA, USA; UMASS Chan Medical School, United States
| | - Karim Alavi
- Department of Surgery, Division of Colorectal Surgery, UMASS Memorial Health, Worcester, MA, USA; UMASS Chan Medical School, United States
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25
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Murphy CC, Zaki TA. Changing epidemiology of colorectal cancer - birth cohort effects and emerging risk factors. Nat Rev Gastroenterol Hepatol 2024; 21:25-34. [PMID: 37723270 DOI: 10.1038/s41575-023-00841-9] [Citation(s) in RCA: 32] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/22/2023] [Indexed: 09/20/2023]
Abstract
Incidence and mortality of colorectal cancer (CRC) are increasing worldwide, suggesting broad changes in the epidemiology of CRC. In this Review, we discuss the changes that are becoming evident, including trends in CRC incidence and mortality by age and birth cohort, and consider the contributions of early-life exposures and emerging risk factors to these changes. Importantly, incidence of CRC has increased among people born since the early 1950s in nearly all regions of the world. These so-called birth cohort effects imply the involvement of factors that influence the earliest stages of carcinogenesis and have effects across the life course. Accumulating evidence supports the idea that early-life exposures are important risk factors for CRC, including exposures during fetal development, childhood, adolescence and young adulthood. Environmental chemicals could also have a role because the introduction of many in the 1950s and 1960s coincides with increasing incidence of CRC among people born during those years. To reverse the expected increases in the global burden of CRC, participation in average-risk screening programmes needs to be increased by scaling up and implementing evidence-based screening strategies, and emerging risk factors responsible for these increases need to be identified.
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Affiliation(s)
- Caitlin C Murphy
- Department of Health Promotion & Behavioral Sciences, University of Texas Health Science Center at Houston (UTHealth Houston) School of Public Health, Houston, TX, USA.
| | - Timothy A Zaki
- Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
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26
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Gholami Chahkand MS, Esmaeilpour Moallem F, Ghasemi-Kebria F, Malekzadeh R, Roshandel G, Taher M. Descriptive Epidemiology of Early-Onset Gastrointestinal Cancers in Iran, 2014-2018. Middle East J Dig Dis 2024; 16:28-33. [PMID: 39050103 PMCID: PMC11264827 DOI: 10.34172/mejdd.2024.365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 12/11/2023] [Indexed: 07/27/2024] Open
Abstract
Background We aim to present incidence rates and geographical distribution of most common early-onset gastrointestinal cancers (EOGICs), including early-onset esophageal cancer (EOEC), gastric cancer (EOGC) and colorectal cancer (EOCRC) in Iran, 2014-2018. Methods Data on new cases of EOEC, EOGC and EOCRC were obtained from publicly available annual reports of the Iranian National Population-based Cancer Registry (INPCR). Incidence rates were calculated using the population data available from the Statistical center of Iran. We considered the World standard population for calculation of age-standardized incidence rates (ASR). We also calculated 95% confidence intervals (CIs) for ASR. All rates are presented per 100000 person-years. Results Overall, 19,679 new cases of EOGIC were registered by the INPCR between 2014 and 2018. The ASRs (95% CI) of EOEC, EOGC and EOCRC were 0.49 (95% CI: 0.47-0.51), 1.67 (1.63-1.71), and 3.07 (3.01-3.13) per 100,000 person-years, respectively. Our findings indicate decreasing and constant trends in the ASR of EOEC and EOGC during the study period, 2014-2018. There was an increasing trend in the ASR of EOCRC. We also found geographical disparities in the incidence rates of EOGICs across provinces of Iran, suggesting the highest ASRs of EOEC in Golestan (1.3), EOGC in Ilam (2.99) and EOCRC in Ilam (4.49). Conclusion Our findings suggested that the incidence rate of EOCRC is consistently increasing. We also found variations in the incidence of EOGICs among different provinces. Further investigations are recommended to clarify the time trends and risk factors of EOGICs in Iran.
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Affiliation(s)
| | - Fatemeh Esmaeilpour Moallem
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Fatemeh Ghasemi-Kebria
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan, Iran
| | - Mohammad Taher
- Division of Gastroenterology and Hepatology, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran
- Liver Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
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27
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Constantinou V, Constantinou C. Focusing on colorectal cancer in young adults (Review). Mol Clin Oncol 2024; 20:8. [PMID: 38125745 PMCID: PMC10729308 DOI: 10.3892/mco.2023.2706] [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: 07/25/2023] [Accepted: 11/07/2023] [Indexed: 12/23/2023] Open
Abstract
Colorectal cancer (CRC) ranks as the third leading cause of cancer-related mortality worldwide. Recent years have witnessed an increase in the incidence of CRC among adults <50 years old on a global scale. The increased incidence is associated with several modifiable risk factors, including obesity, type II diabetes, physical inactivity and frequent antibiotic use. In younger individuals, haematochezia and abdominal pain are the most common symptoms, predominantly affecting the left-side colon. While certain cases of early-onset CRC (eoCRC) are associated with a genetic predisposition, the majority result from sporadic mutations in the genes APC, KRAS, BRAF and TP53, which trigger uncontrolled cell proliferation and tumour formation. Colorectal carcinogenesis involves three major pathways: The chromosomal instability (CIN), microsatellite instability and CpG island methylator phenotype pathways. Dysregulation of the CIN pathway accounts for 85% of sporadic cases of eoCRC. Notably, eoCRC exhibits a distinctive molecular profile, characterized by a decreased prevalence of BRAF mutations, an increased prevalence of KRAS mutations and LINE-1 hypomethylation, and involvement of the Microsatellite and Chromosomal Stable pathway. Prevention strategies for eoCRC primarily centre on lifestyle modifications and the development of screening programs targeting younger populations. Further exploration into the molecular mechanisms involved in the identification of novel risk factors associated with eoCRC is imperative. These efforts, in conjunction with the development of specific screening strategies, hold the potential to reduce morbidity and mortality in the future.
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Affiliation(s)
- Virginia Constantinou
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, CY-1700 Nicosia, Cyprus
| | - Constantina Constantinou
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, CY-1700 Nicosia, Cyprus
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28
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Hameed H, Faheem S, Zaman M, Khan MA, Ghumman SA, Sarwar HS, Mahmood A. Multiomics approaches in cancer. BIOLOGICAL INSIGHTS OF MULTI-OMICS TECHNOLOGIES IN HUMAN DISEASES 2024:53-72. [DOI: 10.1016/b978-0-443-23971-7.00003-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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29
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Griffith BD, Lazarus J, McGue J, Krishnan S, D’Angelica MI, Shia J, Dobrosotskaya I, Shi J, Edwards J, Rao A, Frankel TL. Unique characteristics of the tumor immune microenvironment in young patients with metastatic colorectal cancer. Front Immunol 2023; 14:1289402. [PMID: 38152402 PMCID: PMC10751347 DOI: 10.3389/fimmu.2023.1289402] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Accepted: 11/17/2023] [Indexed: 12/29/2023] Open
Abstract
Introduction Metastatic colorectal cancer (mCRC) remains a common and highly morbid disease, with a recent increase in incidence in patients younger than 50 years. There is an acute need to better understand differences in tumor biology, molecular characteristics, and other age-related differences in the tumor microenvironment (TME). Methods 111 patients undergoing curative-intent resection of colorectal liver metastases were stratified by age into those <50 years or >65 years old, and tumors were subjected to multiplex fluorescent immunohistochemistry (mfIHC) to characterize immune infiltration and cellular engagement. Results There was no difference in infiltration or proportion of immune cells based upon age, but the younger cohort had a higher proportion of programmed death-ligand 1 (PD-L1)+ expressing antigen presenting cells (APCs) and demonstrated decreased intercellular distance and increased cellular engagement between tumor cells (TCs) and cytotoxic T lymphocytes (CTLs), and between TCs and APCs. These trends were independent of microsatellite instability in tumors. Discussion Age-related differences in PD-L1 expression and cellular engagement in the tumor microenvironment of patients with mCRC, findings which were unrelated to microsatellite status, suggest a more active immune microenvironment in younger patients that may offer an opportunity for therapeutic intervention with immune based therapy.
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Affiliation(s)
- Brian D. Griffith
- Department of Surgery, University of Michigan, Ann Arbor, MI, United States
| | - Jenny Lazarus
- Department of Surgery, University of Michigan, Ann Arbor, MI, United States
| | - Jake McGue
- Department of Surgery, University of Michigan, Ann Arbor, MI, United States
| | - Santhoshi Krishnan
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States
- Department of Electrical and Computer Engineering, Rice University, Houston, TX, United States
| | - Michael I. D’Angelica
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Jinru Shia
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, United States
| | - Irina Dobrosotskaya
- Division of Hematology and Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI, United States
| | - Jaiqi Shi
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
| | - Jacob Edwards
- Department of Surgery, University of Michigan, Ann Arbor, MI, United States
| | - Arvind Rao
- Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States
- Department of Electrical and Computer Engineering, Rice University, Houston, TX, United States
- Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United States
- Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States
| | - Timothy L. Frankel
- Department of Surgery, University of Michigan, Ann Arbor, MI, United States
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Wu Y, Luo J, Xu B. Network pharmacology and bioinformatics to identify the molecular mechanisms of Gleditsiae Spina against colorectal cancer. Curr Res Toxicol 2023; 5:100139. [PMID: 38059131 PMCID: PMC10696432 DOI: 10.1016/j.crtox.2023.100139] [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: 08/29/2023] [Revised: 11/14/2023] [Accepted: 11/21/2023] [Indexed: 12/08/2023] Open
Abstract
Objective In this study, network pharmacology, bioinformatics and molecular docking were used to explore the active phytochemicals, hub genes, and potential molecular mechanisms of Gleditsiae Spina in treating of colorectal cancer.. Methods The targets of Gleditsiae Spina, and targets related to CRC were derived from databases. We identified the hub genes for Gleditsiae Spina anti-colorectal cancer following the protein-protein-interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were used to analyze the hub genes from a macro perspective. Finally, we verified the hub genes by molecular docking, GEPIA, HPA, and starBase database. Results We identified nine active phytochemicals and 36 intersection targets. The GO enrichment analysis results showed that Gleditsiae Spina may be involved in gene targets affecting multiple biological processes, including response to radiation, response to ionizing radiation, cyclin-dependent protein kinase holoenzyme complex, serine/threonine protein kinase complex, cyclin-dependent protein serine/threonine kinase regulator activity and protein kinase regulator activity. KEGG enrichment analysis results indicated that the P53 signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway, PI3K-Akt signaling pathway, and JAK-STAT signaling pathway were mainly related to the effect of Gleditsiae Spina on colorectal cancer. Molecular docking analysis suggested that the active phytochemicals of Gleditsiae Spina could combine well with hub genes (PTGS1, PIK3CG, CCND1, CXCL8 and ADRB2). Conclusion This study provides clues for further study of anti-CRC phytochemicals as well as their mechanisms of provides a basis for their development model.
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Affiliation(s)
- Yingzi Wu
- Guangdong Provincial Key Laboratory IRADS and Department of Life Sciences, BNU-HKBU United International College, Zhuhai 519087, China
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Jinhai Luo
- Guangdong Provincial Key Laboratory IRADS and Department of Life Sciences, BNU-HKBU United International College, Zhuhai 519087, China
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
| | - Baojun Xu
- Guangdong Provincial Key Laboratory IRADS and Department of Life Sciences, BNU-HKBU United International College, Zhuhai 519087, China
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Demb J, Liu L, Murphy CC, Doubeni CA, Martinez ME, Gupta S. Time to Endoscopy or Colonoscopy Among Adults Younger Than 50 Years With Iron-Deficiency Anemia and/or Hematochezia in the VHA. JAMA Netw Open 2023; 6:e2341516. [PMID: 37930701 PMCID: PMC10628727 DOI: 10.1001/jamanetworkopen.2023.41516] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/10/2023] [Accepted: 09/24/2023] [Indexed: 11/07/2023] Open
Abstract
Importance To date, the diagnostic test completion rate and the time to diagnostic endoscopy or colonoscopy among adults with iron-deficiency anemia (IDA) and/or hematochezia have not been well characterized. Objective To evaluate the diagnostic test completion rate and the time to diagnostic testing among veterans younger than 50 years with IDA and/or hematochezia. Design, Setting, and Participants This cohort study was conducted within the Veterans Health Administration between October 1, 1999, and December 31, 2019, among US veterans aged 18 to 49 years from 2 separate cohorts: those with a diagnosis of IDA (n = 59 169) and those with a diagnosis of hematochezia (n = 189 185). Statistical analysis was conducted from August 2021 to August 2023. Exposures Diagnostic testing factors included age, sex, race and ethnicity, Veterans Health Administration geographic region, and hemoglobin test value (IDA cohort only). Main Outcomes and Measures Primary outcomes of diagnostic testing were (1) bidirectional endoscopy after diagnosis of IDA and (2) colonoscopy or sigmoidoscopy after diagnosis of hematochezia. The association between diagnostic testing factors and diagnostic test completion was examined using Poisson models. Results There were 59 169 veterans with a diagnosis of IDA (mean [SD] age, 40.7 [7.1] years; 30 502 men [51.6%]), 189 185 veterans with a diagnosis of hematochezia (mean [SD] age, 39.4 [7.6] years; 163 690 men [86.5%]), and 2287 veterans with IDA and hematochezia (mean [SD] age, 41.6 [6.9] years; 1856 men [81.2%]). The cumulative 2-year diagnostic workup completion rate was 22% (95% CI, 22%-22%) among veterans with IDA and 40% (95% CI, 40%-40%) among veterans with hematochezia. Veterans with IDA were mostly aged 40 to 49 years (37 719 [63.7%]) and disproportionately Black (24 480 [41.4%]). Women with IDA (rate ratio [RR], 0.42; 95% CI, 0.40-0.43) had a lower likelihood of diagnostic test completion compared with men with IDA. Black (RR, 0.65; 95% CI, 0.62-0.68) and Hispanic (RR, 0.88; 95% CI, 0.82-0.94) veterans with IDA were less likely to receive diagnostic testing compared with White veterans with IDA. Veterans with hematochezia were mostly White (105 341 [55.7%]). Among veterans with hematochezia, those aged 30 to 49 years were more likely to receive diagnostic testing than adults younger than 30 years of age (age 30-39 years: RR, 1.15; 95% CI, 1.12-1.18; age 40-49 years: RR, 1.36; 95% CI, 1.33-1.40). Hispanic veterans with hematochezia were less likely to receive diagnostic testing compared with White veterans with hematochezia (RR, 0.96; 95% CI, 0.93-0.98). Conclusions and Relevance In the cohorts of veterans younger than 50 years with IDA and/or hematochezia, the diagnostic test completion rate was low. Follow-up was less likely among female, Black, and Hispanic veterans with IDA and Hispanic veterans with hematochezia. Optimizing timely follow-up across social and demographic groups may contribute to improving colorectal cancer outcomes and mitigate disparities.
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Affiliation(s)
- Joshua Demb
- Division of Gastroenterology, Department of Internal Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Lin Liu
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
- Moores Cancer Center, University of California, San Diego, La Jolla
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla
| | - Caitlin C. Murphy
- University of Texas Health Science Center at Houston (UTHealth Houston) School of Public Health, Houston
| | - Chyke A. Doubeni
- Department of Family and Community Medicine of the College of Medicine. Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, Columbus
| | - Maria Elena Martinez
- Moores Cancer Center, University of California, San Diego, La Jolla
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla
| | - Samir Gupta
- Division of Gastroenterology, Department of Internal Medicine, University of California, San Diego, La Jolla
- Jennifer Moreno Veteran Affairs San Diego Healthcare System, San Diego, California
- Moores Cancer Center, University of California, San Diego, La Jolla
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Landay SL, Burns JA, Bickle ML, Baltich Nelson B, Nipp RD. Fertility preservation in reproductive-aged female patients with colorectal cancer: a scoping review. Support Care Cancer 2023; 31:612. [PMID: 37796328 DOI: 10.1007/s00520-023-08081-y] [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: 05/16/2023] [Accepted: 09/26/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND Colorectal cancer (CRC) incidence in adults younger than 50 years is steadily increasing in the USA, and treatment for CRC can impact future fertility. However, fertility decision-making in female patients with CRC can be complex, with fertility preservation (FP) counseling occurring inconsistently. PURPOSE The goal of this scoping review was to assess the literature regarding the frequency and quality of fertility preservation (FP) discussions taking place among oncology clinicians and their reproductive-age female patients with colorectal cancer (CRC) in order to identify existing gaps in care and inform future research, interventions, or potential changes in practice. METHODS A comprehensive literature search was conducted using the Ovid Medline, PsycInfo, and Scopus databases in order to identify studies pertaining to FP counseling in reproductive-age female patients with CRC. We used Covidence to screen studies for relevance and to extract data. Findings of interest included rate of fertility and/or FP discussions, patient characteristics associated with fertility discussions, initiators of discussions, rate of referrals to fertility specialists, patient utilization of FP services, and unmet fertility needs. We performed both quantitative and qualitative data synthesis. RESULTS We identified five studies that met our inclusion criteria, all published between 2007 and 2022. Frequency of fertility counseling discussions was low across studies, with a range of 15 to 52.5% of female patients with CRC receiving counseling. Patient characteristics which may be associated with likelihood of fertility discussion included age, parity, number of children, cancer location and stage, treatment type, and quality of life. The literature suggested that fertility discussions were initiated by clinicians about two-thirds of the time, and medical oncologists were the clinicians most likely to initiate. Studies did capture unmet fertility-related patient needs; participants who did not receive counseling often expressed desire for these discussions and regret that they did not occur. CONCLUSION Despite increasing incidence of CRC in patients at younger ages, this scoping review found a dearth of research conducted on young female CRC patients' experiences with fertility counseling and referrals. Notably, the existing research reveals that relatively few of these patients are receiving appropriate counseling. Additional research is needed to clarify current FP counseling practices, patient and clinician perceptions about FP, and ways to improve the quantity and quality of FP counseling in this patient population.
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Affiliation(s)
- Sophia L Landay
- Department of Obstetrics and Gynecology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
| | - Jamie A Burns
- Department of Obstetrics and Gynecology, Lenox Hill Hospital-Northwell Health, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA
| | - Madison L Bickle
- OU Health Stephenson Cancer Center, University of Oklahoma College of Medicine, Oklahoma City, OK, USA
| | | | - Ryan D Nipp
- OU Health Stephenson Cancer Center, University of Oklahoma College of Medicine, Oklahoma City, OK, USA
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Perea J, Gallagher P, Delores A. Lights and shadows in the early-onset colorectal cancer management and research: An integrative perspective - Physician scientist with patient advocates. Best Pract Res Clin Gastroenterol 2023; 66:101851. [PMID: 37852716 DOI: 10.1016/j.bpg.2023.101851] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 05/27/2023] [Accepted: 07/04/2023] [Indexed: 10/20/2023]
Abstract
Early-onset colorectal cancer (age under 50 years) (EOCRC) is an entity of undeniable importance, both because of its growing incidence, and the population it affects. Other current reviews emphasize the essential points regarding the clinical management and knowledge of its molecular bases. However, we intend to go one step further. With the increased significance of patient participation and disease experience in mind, we have integrated the voice of the patient to show the weaknesses and the needs, and next steps in the advancement of knowledge and management of EOCRC. This integrative review of the different perspectives, clinical, research and the patients themselves, can therefore be defined as an integrative needs assessment. Hence, this may be a first step in working towards an essential homogeneity of definitions and action.
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Affiliation(s)
- José Perea
- Biomedical Research Institute of Salamanca (IBSAL), Salamanca, Spain; Department of Surgery. Vithas Arturo Soria University Hospital, Madrid, Spain.
| | | | - Annie Delores
- Fight Colorectal Cancer, USA; KRAS Kickers, USA; Colon Cancer Stars, USA
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Imran M, Baig M, Alshuaibi RO, Almohammadi TA, Albeladi SA, Zaafarani FTM. Knowledge and awareness about colorectal cancer and barriers to its screening among a sample of general public in Saudi Arabia. PLoS One 2023; 18:e0290269. [PMID: 37611015 PMCID: PMC10446202 DOI: 10.1371/journal.pone.0290269] [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: 03/26/2023] [Accepted: 08/04/2023] [Indexed: 08/25/2023] Open
Abstract
INTRODUCTION The present study investigated knowledge, awareness, and barriers to colorectal cancer (CRC) screening from a sample of the general population in Saudi Arabia. METHODS This cross-sectional study was conducted between August 2022 and January 2023 among a sample of the general population in Jeddah, Saudi Arabia. The questionnaire consisted of demographics, knowledge and awareness, and questions about CRC screening barriers. RESULTS A total of 1105 adults belonged to the general public [505 females (45.7%) and 600 males (54.3%)] recruited in this survey. The mean age of the respondents was 39.79±12.49. The internet was the primary source of CC information for most participants, 661(59.8%). Gender-wise comparison of general public responses regarding CRC knowledge and awareness and barriers to screening showed a mixed response. Analysis of participants' knowledge regarding CRC and its risk factors and warning signs showed that 356(32.2%) people believed that the best age for the CRC test is 41-50 years, and 285(25.8%) responded they don't know. Almost half of the participants, 539(48.8%), were not interested in attending awareness seminars about CRC, while 371(33.6%) were interested in attending awareness seminars about CRC. Only one-third of the respondents, 368(33.3%), knew of any tests or examinations used to detect CRC. Participants' perceptions about colonoscopy-related and FOBT-related barriers to CRC screening disclosed that these are time-consuming, expensive, painful, embarrassing, etc. CONCLUSION Insufficient information, poor awareness, and several assumed barriers to CRC screening were found among study participants. There is a need to close knowledge gaps and offer them comprehensive information regarding CRC, as well as the availability and benefits of screening. In this aspect, social media can be extremely beneficial.
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Affiliation(s)
- Muhammad Imran
- Department of Surgery, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mukhtiar Baig
- Department of Clinical Biochemistry, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia
| | | | | | - Samah Abdulsalam Albeladi
- 6 Year Medical Student, Faculty of Medicine in Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia
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Foppa C, Maroli A, Luberto A, La Raja C, Spaggiari P, Bonifacio C, De Zanet S, Montorsi M, Piscuoglio S, Terracciano LM, Santoro A, Spinelli A. Early Age of Onset Is an Independent Predictor for a Worse Response to Neoadjuvant Therapies in Sporadic Rectal Cancer Patients. Cancers (Basel) 2023; 15:3750. [PMID: 37509411 PMCID: PMC10378654 DOI: 10.3390/cancers15143750] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/15/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023] Open
Abstract
The incidence of rectal cancer (RC) is increasing in the population aged ≤ 49 (early-onset RC-EORC). EORC patients are more likely to present with locally advanced disease at diagnosis than late-onset RC (LORC; aged ≥ 50) patients. As a consequence, more EORC patients undergo neoadjuvant therapies. The response to treatment in EORC patients is still unknown. This study aims to explore the effect of age of onset on the pathological response to neoadjuvant therapies in sporadic locally advanced RC (LARC) patients. Based on an institutional prospectively maintained database, LARC patients undergoing neoadjuvant therapies and radical surgery between January 2010 and December 2022 were allocated to the EORC and LORC groups. The primary endpoint was the rate of incomplete response (Dworak 0-2). A total of 326 LORC and 79 EORC patients were included. Pre-neoadjuvant tumor features were comparable. A significantly higher rate of incomplete response was observed in EORC patients (49% vs. 35%; p = 0.028). From multivariable analysis, early age of onset, smoking and extramural invasion presented as independent risk factors for a worse response. This study demonstrates that an early age of onset is related to a worse response and calls for different multimodal strategies in this group of patients.
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Affiliation(s)
- Caterina Foppa
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Annalisa Maroli
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Antonio Luberto
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Carlotta La Raja
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Paola Spaggiari
- Division of Pathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Cristiana Bonifacio
- Division of Diagnostic Radiology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Stefano De Zanet
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Marco Montorsi
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy
- Division of General and Digestive Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Salvatore Piscuoglio
- Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, 4001 Basel, Switzerland
- Department of Biomedicine, University Hospital Basel, University of Basel, 4001 Basel, Switzerland
| | - Luigi Maria Terracciano
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy
- Division of Pathology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Armando Santoro
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy
- Division of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Via Rita Levi Montalcini 4, 20090 Milan, Italy
- Division of Colon and Rectal Surgery, IRCCS Humanitas Research Hospital, Via Manzoni 56, 20089 Milan, Italy
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Dikeocha IJ, Al-Kabsi AM, Ahmeda AF, Mathai M, Alshawsh MA. Investigation into the Potential Role of Propionibacterium freudenreichii in Prevention of Colorectal Cancer and Its Effects on the Diversity of Gut Microbiota in Rats. Int J Mol Sci 2023; 24:ijms24098080. [PMID: 37175785 PMCID: PMC10179204 DOI: 10.3390/ijms24098080] [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: 12/31/2022] [Revised: 02/19/2023] [Accepted: 02/21/2023] [Indexed: 05/15/2023] Open
Abstract
Colorectal cancer (CRC) accounts for 10% of all cancer diagnoses and cancer-related deaths worldwide. Over the past two decades, several studies have demonstrated the clinical benefits of probiotic supplementation and some studies have shown that certain probiotics can modulate immunity and strengthen gut microbiota diversity. This study aims to assess the impact of the Propionibacterium freudenreichii (PF) probiotic against CRC induced by azoxymethane (AOM), and to investigate its effects on gut microbiota diversity in rats, as well as to evaluate the anti-proliferative activities of PF in HCT116 CRC cells. This experiment was performed using four groups of SD rats: normal control, AOM group, PF group (1 × 109 CFU/mL), and standard drug control (5-fluorouracil, 35 mg/kg). Methylene blue staining of colon tissues showed that the administration of PF significantly reduced the formation of colonic aberrant crypt foci (ACF) compared to the AOM control group. In addition, treated rats had lower levels of malondialdehyde in their colon tissue homogenates, indicating that lipid peroxidation was suppressed by PF supplementation. Furthermore, 16S rRNA gene analysis revealed that probiotic treatment enhanced the diversity of gut microbiota in rats. In vitro study showed that the viability of HCT116 cells was inhibited by the probiotic cell-free supernatant with an IC50 value of 13.3 ± 0.133. In conclusion, these results reveal that consuming PF as probiotic supplements modulates gut microbiota, inhibits the carcinogenic effects of AOM, and exerts anti-proliferative activity against CRC cells. Further studies are required to elucidate the role of PF on the immune response during the development and growth of CRC.
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Affiliation(s)
| | | | - Ahmad Faheem Ahmeda
- Department of Basic Medical Sciences, College of Medicine, Ajman University, Ajman P.O. Box 346, United Arab Emirates
- Center of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates
| | - Michael Mathai
- College of Health and Biomedicine, Victoria University, Melbourne, VIC 3011, Australia
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Yu J, Sun Q, Hui Y, Xu J, Shi P, Chen Y, Chen Y. Vitamin D receptor prevents tumour development by regulating the Wnt/β-catenin signalling pathway in human colorectal cancer. BMC Cancer 2023; 23:336. [PMID: 37046222 PMCID: PMC10091620 DOI: 10.1186/s12885-023-10690-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 02/28/2023] [Indexed: 04/14/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a common disease threatening human lives worldwide, and vitamin D receptor (VDR) contributes protective roles in this disease. However, the molecular mechanisms underlying VDR protection in CRC progression require further investigation. METHODS In this study, we statistically analyzed the relationship between VDR expression and CRC development in patients and detected invasion and apoptosis in CRC cells with VDR overexpression and interference. We also detected the expression of key genes involved in Wnt/β-catenin signalling (β-catenin, lymphoid enhancer factor (LEF)-1 and cyclin D1) in SW480 cells and nude mice injected with VDR-overexpressing SW480 cells and observed tumour development. Additionally, we performed Co-immunoprecipitation (Co-IP) and glutathione-S-transferase (GST) pull-down assays to identify the protein interactions of VDR with β-catenin, dual luciferase (LUC) and chromatin immunoprecipitation (ChIP) to detect the activation of LEF-1 by VDR. RESULTS The VDR level was closely related to the development and prognosis of CRC patients. VDR overexpression inhibited invasion but promoted apoptosis in cancer cells. β-catenin shRNA contributed oppositely to cancer cell activity with VDR shRNA. Additionally, VDR interacted with β-catenin at the protein level and blocked its nuclear accumulation. VDR regulated the expression of β-catenin, cyclin D1 and LEF-1 and directly activated LEF-1 transcription in vitro. Furthermore, nude mice injected with VDR-overexpressing SW480 cells revealed suppression of tumour growth and decreased expression of β-catenin, cyclin D1 and LEF-1. CONCLUSIONS This study indicated that VDR protected against CRC disease in humans by inhibiting Wnt/β-catenin signalling to control cancer cell invasion and apoptosis, providing new evidence to explore VDR biomarkers or agonists for CRC patient diagnosis and treatment.
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Affiliation(s)
- Jie Yu
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Qi Sun
- Department of Pathology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China
| | - Yi Hui
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Jinping Xu
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Pancheng Shi
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Yu Chen
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China
| | - Yunzhao Chen
- Department of Pathology, The People's Hospital of Suzhou New District, No. 95, Huashan Road, High Tech Zone, Suzhou, Jiangsu Prov, China.
- Department of Pathology, Zhejiang Provincial People's Hospital, Hangzhou, China.
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Perez-Mayoral J, Gonzalez-Pons M, Centeno-Girona H, Montes-Rodríguez IM, Soto-Salgado M, Suárez B, Rodríguez N, Colón G, Sevilla J, Jorge D, Llor X, Xicola RM, Toro DH, Tous-López L, Torres-Torres M, Reyes JS, López-Acevedo N, Goel A, Rodríguez-Quilichini S, Cruz-Correa M. Molecular and Sociodemographic Colorectal Cancer Disparities in Latinos Living in Puerto Rico. Genes (Basel) 2023; 14:894. [PMID: 37107652 PMCID: PMC10138302 DOI: 10.3390/genes14040894] [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: 02/15/2023] [Revised: 04/05/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND The incidence of sporadic colorectal cancer (CRC) among individuals <50 years (early-onset CRC) has been increasing in the United States (U.S.) and Puerto Rico. CRC is currently the leading cause of cancer death among Hispanic men and women living in Puerto Rico (PRH). The objective of this study was to characterize the molecular markers and clinicopathologic features of colorectal tumors from PRH to better understand the molecular pathways leading to CRC in this Hispanic subpopulation. METHODS Microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF mutation status were analyzed. Sociodemographic and clinicopathological characteristics were evaluated using Chi-squared and Fisher's exact tests. RESULTS Of the 718 tumors analyzed, 34.2% (n = 245) were early-onset CRC, and 51.7% were males. Among the tumors with molecular data available (n = 192), 3.2% had MSI, 9.7% had BRAF, and 31.9% had KRAS mutations. The most common KRAS mutations observed were G12D (26.6%) and G13D (20.0%); G12C was present in 4.4% of tumors. A higher percentage of Amerindian admixture was significantly associated with early-onset CRC. CONCLUSIONS The differences observed in the prevalence of the molecular markers among PRH tumors compared to other racial/ethnic groups suggest a distinct molecular carcinogenic pathway among Hispanics. Additional studies are warranted.
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Affiliation(s)
| | - Maria Gonzalez-Pons
- University of Puerto Rico Comprehensive Cancer Center, San Juan, PR 00936, USA
| | | | | | | | - Belisa Suárez
- University of Puerto Rico Comprehensive Cancer Center, San Juan, PR 00936, USA
| | - Natalia Rodríguez
- School of Medicine, Universidad Central del Caribe, Bayamon, PR 00956, USA
| | - Giancarlo Colón
- School of Medicine, Universidad Central del Caribe, Bayamon, PR 00956, USA
| | - Javier Sevilla
- School of Medicine, Universidad Central del Caribe, Bayamon, PR 00956, USA
| | - Daphne Jorge
- School of Medicine, Ponce Health Sciences University, Ponce, PR 00716, USA
| | - Xavier Llor
- Department of Internal Medicine and Digestive Diseases, School of Medicine, Yale University, New Haven, CT 06520, USA
| | - Rosa M. Xicola
- Department of Internal Medicine and Digestive Diseases, School of Medicine, Yale University, New Haven, CT 06520, USA
| | - Doris H. Toro
- VA Caribbean Healthcare System, San Juan, PR 00921, USA
| | - Luis Tous-López
- Ashford Presbyterian Community Hospital, San Juan, PR 00907, USA
| | | | - José S. Reyes
- Ashford Presbyterian Community Hospital, San Juan, PR 00907, USA
| | | | - Ajay Goel
- Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA
| | | | - Marcia Cruz-Correa
- University of Puerto Rico Comprehensive Cancer Center, San Juan, PR 00936, USA
- Department of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PR 00935, USA
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Marx O, Mankarious M, Yochum G. Molecular genetics of early-onset colorectal cancer. World J Biol Chem 2023; 14:13-27. [PMID: 37034132 PMCID: PMC10080548 DOI: 10.4331/wjbc.v14.i2.13] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/20/2022] [Accepted: 02/13/2023] [Indexed: 03/24/2023] Open
Abstract
Early-onset colorectal cancer (EOCRC) has been rising in global prevalence and incidence over the past several decades. Environmental influences, including generational lifestyle changes and rising obesity, contribute to these increased rates. While the rise in EOCRC is best documented in western countries, it is seen throughout the world, although EOCRC may have distinct genetic mutations in patients of different ethnic backgrounds. Pathological and molecular characterizations show that EOCRC has a distinct presentation compared with later-onset colorectal cancer (LOCRC). Recent studies have identified DNA, RNA, and protein-level alterations unique to EOCRC, revealing much-needed biomarkers and potential novel therapeutic targets. Many molecular EOCRC studies have been performed with Caucasian and Asian EOCRC cohorts, however, studies of other ethnic backgrounds are limited. In addition, certain molecular characterizations that have been conducted for LOCRC have not yet been repeated in EOCRC, including high-throughput analyses of histone modifications, mRNA splicing, and proteomics on large cohorts. We propose that the complex relationship between cancer and aging should be considered when studying the molecular underpinnings of EOCRC. In this review, we summarize current EOCRC literature, focusing on sporadic molecular alterations in tumors, and their clinical implications. We conclude by discussing current challenges and future directions of EOCRC research efforts.
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Affiliation(s)
- Olivia Marx
- Department of Biochemistry & Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
| | - Marc Mankarious
- Department of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University Milton S. Hershey Medical Center, Hershey, PA 17033, United States
| | - Gregory Yochum
- Department of Biochemistry & Molecular Biology & Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, United States
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Ye X, Han P, Wu Z, Cui Y, Chen Y, Chen Z, Gao Q. New management of surveillance in patients with baseline serrated polyps: a large single-center retrospective cohort study in China. Eur J Gastroenterol Hepatol 2023; 35:181-190. [PMID: 36574309 DOI: 10.1097/meg.0000000000002494] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
BACKGROUND Serrate d polyps (SP) is associated with an increased risk of colorectal cancer. Patients with SP history tend to have SP recurrence. However, the risk factors for metachronous polyps (MP) in those patients are not well established. METHODS Data of colonoscopy were retrospectively reviewed from October 2012 to October 2021. The pathology database, electronic medical records and telephone follow-up data were also observed. RESULTS A total of 906 patients were studied including 278 patients with MPs and 628 patients without. The multiplicity of polyps (OR, 13.63; 95% CI, 8.80-21.75), older age (OR, 5.71; 95% CI, 1.87-20.63), abdominal obesity (OR, 2.46; 95% CI, 0.98-6.42), current smoker (OR, 2.93; 95% CI, 1.15-7.83) and sedentary lifestyle (OR, 1.41; 95% CI, 1.22-1.65) are significantly associated with the risk of MPs. Patients with baseline SP < 10 mm were more likely to develop higher or same risk-grade polyps (HSRGP) ( P = 0.0014). Patients with non-clinically significant SPs whether coexisted with adenoma or not were more likely to develop HSRGPs when compared to others ( P < 0.001). CONCLUSION Total number of polyps, older age, sedentary behavior, abdominal obesity and smoking status contributed to the risk of MPs at surveillance colonoscopy. Patients with grade 1 SPs might require closer surveillance. SPs coexisting with conventional adenoma did not increase the risk of MPs but may increase the risk of developing HSRGPs.
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Affiliation(s)
- Xiangxi Ye
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health
| | - Peiyi Han
- Department of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhijie Wu
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health
| | - Yun Cui
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health
| | - Yingxuan Chen
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health
| | - Zhaofei Chen
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health
| | - Qinyan Gao
- Division of Gastroenterology and Hepatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology & Hepatology, Ministry of Health
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Li M, Vega EA, Mellado S, Salehi O, Kozyreva O, Conrad C. Colorectal cancer in young patients below screening age - Demographic and socioeconomic factors associated with incidence and survival. Surg Oncol 2023; 46:101906. [PMID: 36738697 DOI: 10.1016/j.suronc.2023.101906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 12/23/2022] [Accepted: 01/22/2023] [Indexed: 02/03/2023]
Abstract
BACKGROUND While early onset colorectal cancer (EOCRC) has previously been defined as CRC in patients younger than age 50, recent screening guidelines have been lowered to 45. With more younger patients aged 45-50 are now being screened, incidence trend and outcomes of very early EOCRC (20-44) remains unclear. METHOD Surveillance, Epidemiology, and End Results database was analyzed between 2006 and 2016 using Joinpoint tool to evaluate annual percentage change (APC) in incident rates, focusing on race/ethnicity and socioeconomic status (SES). Cancer specific survival (CSS) was assessed using univariate and multivariate analysis. RESULTS 41,815 EOCRC patients met inclusion criteria. Incidence has increased significantly in both age groups (APC in age group 20-44 = 1.21 and 45-49 = 1.06). Increase incidence of very early EOCRC was observed in White and Hispanic racial/ethnic groups (ACP 1.68 and 2.63), as well as population from counties with high poverty, unemployment, language barrier, foreign born resident, and high school dropout rates (ACP 2.07, 1.87, 1.21, 1.28 and 2.02 respectively). Further, the 5-year CSS was worse in Black patients, and patients from counties with high poverty, unemployment and high school dropouts rates (Age group 20-44, 63.11%, 66.39%, 67.48% and 66.95% respectively). On multivariate analysis, living in high poverty counties was an independent risk factor for poorer CSS for very early EOCRC (HR 1.20, 95% CI 1.07-1.34, p = 0.002). Multivariate analysis was adjusted by sex, pathology type, site of disease, disease extension and surgical treatment history. CONCLUSION Very early EOCRC incidence increases in White, Hispanic and poor patients, and outcomes are worse for minority and low-income patients. Further study on very early EOCRC is needed among those patients.
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Affiliation(s)
- Mu Li
- Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Boston, MA, USA
| | - Eduardo A Vega
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | | | - Omid Salehi
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
| | - Olga Kozyreva
- Dana-Farber Cancer Institute at St. Elizabeth's Medical Center, Boston, MA, USA
| | - Claudius Conrad
- Department of Surgery, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA.
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Early Onset Colorectal Cancer in Arabs, Are We Dealing with a Distinct Disease? Cancers (Basel) 2023; 15:cancers15030889. [PMID: 36765846 PMCID: PMC9913248 DOI: 10.3390/cancers15030889] [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: 12/24/2022] [Revised: 01/23/2023] [Accepted: 01/26/2023] [Indexed: 02/05/2023] Open
Abstract
Early-onset colorectal cancer (EOCRC) incidence is increasing worldwide. Efforts are directed to understand the biological and clinical signatures of EOCRC compared to late-onset colorectal cancer (LOCRC). EOCRC is thought to present differently across different ethnic groups and geographical regions. This study was an attempt to contribute with data from the Arab world toward the understanding of the clinicopathological parameters of EOCRC compared to LOCRC. Data from 254 CRC patients diagnosed at Sultan Qaboos University Hospital from the period 2015-2020 were studied. About 32.6% of all diagnosed CRC patients are below 50 years old, with no differences in gender distribution between EOCRC and LOCRC (p-value 0.417). Rectal involvement and tumor laterality were comparable among the two groups. Adenocarcinoma accounts for 83.3% and 94.2% of EOCRC and LOCRC, respectively. More mucinous and signet ring adenocarcinoma (8.3% each) were reported in EOCRC than LOCRC (2.9% and 2.2%, respectively). MLH1 and PMS2 loss are more common among LOCRC, but MSH6 loss is more frequent in EOCRC. The overall survival of EOCRC and LOCRC was comparable (median survival 64.88 and 67.24 months, respectively). This study showed comparable clinicopathological parameters between EOCRC and LOCRC from Arabs, which adds to the bigger picture of understand the disease.
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Pucci MD, Dasenbrock A, Tanzawa CK, Santos MBD. Perfil Clínico-Epidemiológico do Câncer Colorretal na Região Oeste do Paraná, Brasil, 2016-2018. REVISTA BRASILEIRA DE CANCEROLOGIA 2023. [DOI: 10.32635/2176-9745.rbc.2023v69n1.3143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
Introdução: O câncer colorretal é a neoplasia mais frequente do trato gastrointestinal, sendo a segunda principal causa de morte por câncer no mundo. Objetivo: Traçar um perfil clínico-epidemiológico do câncer colorretal na Região Oeste do Paraná (Brasil), entre 2016 e 2018. Método: Estudo observacional analítico do tipo transversal, construído a partir da análise de resultados de exames anatomopatológicos, realizados entre 2016 a 2018. Realizaram-se análises por estatística descritiva, teste de associação qui-quadrado e U de Mann-Whitney. Adotou-se nível de significância de 5%. Resultados: A análise de 509 laudos positivos para câncer colorretal permitiu identificar o predomínio de pacientes do sexo masculino e a idade média de diagnóstico de 62 anos. A malignidade mostrou-se mais incidente na faixa etária de 61 a 70 anos (29,9%), e considerável número de casos ocorreu em pacientes abaixo de 50 anos (19,6%). Houve predomínio em cólon esquerdo e do tipo histológico adenocarcinoma infiltrativo moderadamente diferenciado. Verificou-se associação entre topografia da doença e sexo, com maior predominância do sexo feminino para tumores do cólon direito e do sexo masculino para tumores do cólon esquerdo (p=0,0081). Conclusão: A partir deste estudo, delineia-se um perfil clínico-epidemiológico do câncer colorretal na Região Oeste do Paraná, com maior incidência da doença em homens, sexagenários, além de predomínio de tumores em cólon esquerdo e do tipo adenocarcinoma infiltrativo moderadamente diferenciado. Tais achados são relevantes considerando a possibilidade de aplicação assertiva de protocolos internacionais de rastreio do câncer nessa população.
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Liu Y, Zhang C, Wang Q, Wu K, Sun Z, Tang Z, Zhang B. Temporal Trends in the Disease Burden of Colorectal Cancer with Its Risk Factors at the Global and National Level from 1990 to 2019, and Projections Until 2044. Clin Epidemiol 2023; 15:55-71. [PMID: 36659904 PMCID: PMC9842526 DOI: 10.2147/clep.s388323] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Accepted: 01/05/2023] [Indexed: 01/13/2023] Open
Abstract
Background This study aimed to evaluate the global colorectal cancer(CRC) trend and the relevant risk factors from 1990 to 2019 and for better policymaking and resource allocation. Methods Data on CRC, including incidence, mortality and disability adjusted life year (DALY) rates, were extracted from the 2019 Global Burden of Disease (GBD) study. The estimated annual percentage changes (EAPCs) were calculated to assess the temporal trend of incidence, mortality and DALYs. The Bayesian age-period-cohort model(BAPC) was used to predict the future burden of CRC. Results In 2019, a total of 2.17 million CRC cases were reported worldwide, a 157% increase from 1990. In high-social demographic index (SDI) regions, the trend of age-standardized incidence rate(ASIR) tended to decrease, while the proportion of people under 50 years of age tended to increase. Although the number of deaths and DALYs increased, the age-standardized death rate (ASDR) and age-standardized DALY rate decreased. The CRC burden was growing fastest in middle-SDI regions, especially in East Asia, followed by low SDI regions. In addition, the milk intake, High-BMI and high fasting plasma glucose play a more important role in on CRC. The predicted cases and deaths in global continued to increase to 2044. And there is an upward trend in ASIR for both men and women. Conclusion In developed regions, the CRC burden continues to decrease, while the CRC burden become more and more severe in developing regions. Overall, the burden of CRC will rising in the near future. Therefore, reasonable resource allocation and prevention policies should be implemented. Developing countries needs more attention.
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Affiliation(s)
- Yang Liu
- The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, 322000, People’s Republic of China
| | - Chao Zhang
- Center for Evidence-Based Medicine and Clinical Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China
| | - Qianwen Wang
- The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, 322000, People’s Republic of China
| | - Kangze Wu
- The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China
| | - Zhouyi Sun
- The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, 322000, People’s Republic of China
| | - Zhe Tang
- The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, Zhejiang, 322000, People’s Republic of China
| | - Bo Zhang
- The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310000, People’s Republic of China,Correspondence: Bo Zhang, The Second Affiliated Hospital, Zhejiang University School of Medicine, 88 Jiefang Road, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel/Fax +86-0571-87783563, Email
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Rausch WD, Fu S, Qin SL. Chinese herb formulae inhibit the proliferation of human colon cancer SW480 cells by inducing cell apoptosis. WORLD JOURNAL OF TRADITIONAL CHINESE MEDICINE 2023. [DOI: 10.4103/2311-8571.369650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023] Open
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Cancer secretome: finding out hidden messages in extracellular secretions. Clin Transl Oncol 2022; 25:1145-1155. [PMID: 36525229 DOI: 10.1007/s12094-022-03027-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/23/2022] [Indexed: 12/23/2022]
Abstract
Secretome analysis has gained popularity recently as a very well-designed proteomic approach that is being used to study various interactions and their effects on cellular activity. This analysis is especially helpful while studying the effects of the cells on their microenvironment, paracrine and autocrine processes, their therapeutic purposes, and as a new diagnostic perspective. Cancer is a condition rather than a specific type of disease and is still yet to be fully understood. Cancer secretome is a fairly new concept that is being implemented to examine the interactions taking place in the tumor microenvironment and can help to understand the phenomena like induction of tumorigenesis, stimulation of immune cells, etc. The secretome analysis helps to gain a different perspective on the existing knowledge on cancer and its effects. The recent advances in secretome studies are directed toward secreted components as drug targets, biomarkers, and companion tools for diagnostic and prognostic purposes in cancer. This review aims to find the interactors in different types of cancer and understand the existing unstructured secretome data and its application in prognosis, diagnosis, and in biomarker study.
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Wu J, Zhang L, Kuchi A, Otohinoyi D, Hicks C. CpG Site-Based Signature Predicts Survival of Colorectal Cancer. Biomedicines 2022; 10:biomedicines10123163. [PMID: 36551919 PMCID: PMC9776399 DOI: 10.3390/biomedicines10123163] [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: 10/29/2022] [Revised: 11/26/2022] [Accepted: 11/28/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND A critical unmet medical need in clinical management of colorectal cancer (CRC) pivots around lack of noninvasive and or minimally invasive techniques for early diagnosis and prognostic prediction of clinical outcomes. Because DNA methylation can capture the regulatory landscape of tumors and can be measured in body fluids, it provides unparalleled opportunities for the discovery of early diagnostic and prognostics markers predictive of clinical outcomes. Here we investigated use of DNA methylation for the discovery of potential clinically actionable diagnostic and prognostic markers for predicting survival in CRC. METHODS We analyzed DNA methylation patterns between tumor and control samples to discover signatures of CpG sites and genes associated with CRC and predictive of survival. We conducted functional analysis to identify molecular networks and signaling pathways driving clinical outcomes. RESULTS We discovered a signature of aberrantly methylated genes associated with CRC and a signature of thirteen (13) CpG sites predictive of survival. We discovered molecular networks and signaling pathways enriched for CpG sites likely to drive clinical outcomes. CONCLUSIONS The investigation revealed that CpG sites can predict survival in CRC and that DNA methylation can capture the regulatory state of tumors through aberrantly methylated molecular networks and signaling pathways.
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Affiliation(s)
- Jiande Wu
- Department of Genetics and the Bioinformatics and Genomics Program, School of Medicine, Louisiana State University Health Sciences Center, Bolivar 533, New Orleans, LA 70112, USA
| | - Lu Zhang
- Department of Public Health Sciences, Clemson University, Clemson, SC 29634, USA
| | - Aditi Kuchi
- Department of Genetics and the Bioinformatics and Genomics Program, School of Medicine, Louisiana State University Health Sciences Center, Bolivar 533, New Orleans, LA 70112, USA
| | - David Otohinoyi
- Department of Genetics and the Bioinformatics and Genomics Program, School of Medicine, Louisiana State University Health Sciences Center, Bolivar 533, New Orleans, LA 70112, USA
| | - Chindo Hicks
- Department of Genetics and the Bioinformatics and Genomics Program, School of Medicine, Louisiana State University Health Sciences Center, Bolivar 533, New Orleans, LA 70112, USA
- Correspondence:
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Jiang X, Jiang Z, Cheng Q, Sun W, Jiang M, Sun Y. Cholecystectomy promotes the development of colorectal cancer by the alternation of bile acid metabolism and the gut microbiota. Front Med (Lausanne) 2022; 9:1000563. [PMID: 36213655 PMCID: PMC9540502 DOI: 10.3389/fmed.2022.1000563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 09/06/2022] [Indexed: 12/24/2022] Open
Abstract
The incidence and mortality of colorectal cancer (CRC) have been markedly increasing worldwide, causing a tremendous burden to the healthcare system. Therefore, it is crucial to investigate the risk factors and pathogenesis of CRC. Cholecystectomy is a gold standard procedure for treating symptomatic cholelithiasis and gallstone diseases. The rhythm of bile acids entering the intestine is altered after cholecystectomy, which leads to metabolic disorders. Nonetheless, emerging evidence suggests that cholecystectomy might be associated with the development of CRC. It has been reported that alterations in bile acid metabolism and gut microbiota are the two main reasons. However, the potential mechanisms still need to be elucidated. In this review, we mainly discussed how bile acid metabolism, gut microbiota, and the interaction between the two factors influence the development of CRC. Subsequently, we summarized the underlying mechanisms of the alterations in bile acid metabolism after cholecystectomy including cellular level, molecular level, and signaling pathways. The potential mechanisms of the alterations on gut microbiota contain an imbalance of bile acid metabolism, cellular immune abnormality, acid-base imbalance, activation of cancer-related pathways, and induction of toxin, inflammation, and oxidative stress.
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Affiliation(s)
- Xi Jiang
- Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Zhongxiu Jiang
- Department of Oncology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Qi Cheng
- Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Wei Sun
- Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
| | - Min Jiang
- Department of Gastroenterology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China
| | - Yan Sun
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China
- *Correspondence: Yan Sun,
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Marx OM, Mankarious MM, Eshelman MA, Ding W, Koltun WA, Yochum GS. Transcriptome Analyses Identify Deregulated MYC in Early Onset Colorectal Cancer. Biomolecules 2022; 12:1223. [PMID: 36139061 PMCID: PMC9496520 DOI: 10.3390/biom12091223] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Revised: 08/23/2022] [Accepted: 08/30/2022] [Indexed: 11/21/2022] Open
Abstract
Despite a global decrease in colorectal cancer (CRC) incidence, the prevalence of early-onset colorectal cancer (EOCRC), or those occurring in individuals before the age of 50, has steadily increased over the past several decades. When compared to later onset colorectal cancer (LOCRC) in individuals over 50, our understanding of the genetic and molecular underpinnings of EOCRCs is limited. Here, we conducted transcriptomic analyses of patient-matched normal colonic segments and tumors to identify gene expression programs involved in carcinogenesis. Amongst differentially expressed genes, we found increased expression of the c-MYC proto-oncogene (MYC) and its downstream targets in tumor samples. We identified tumors with high and low differential MYC expression and found patients with high-MYC tumors were older and overweight or obese. We also detected elevated expression of the PVT1 long-non-coding RNA (lncRNA) in most tumors and found gains in copy number for both MYC and PVT1 gene loci in 35% of tumors evaluated. Our transcriptome analyses indicate that EOCRC can be sub-classified into groups based on differential MYC expression and suggest that deregulated MYC contributes to CRCs that develop in younger patients.
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Affiliation(s)
- Olivia M. Marx
- Department of Biochemistry & Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Department of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Marc M. Mankarious
- Department of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Melanie A. Eshelman
- Department of Pediatrics, Division of Hematology & Oncology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Wei Ding
- Department of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Walter A. Koltun
- Department of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
| | - Gregory S. Yochum
- Department of Biochemistry & Molecular Biology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
- Department of Surgery, Division of Colon & Rectal Surgery, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
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Hong Z, Li Y, Deng X, Chen M, Pan J, Chen Z, Zhang X, Wang C, Qiu C. Comprehensive analysis of triphenyl phosphate: An environmental explanation of colorectal cancer progression. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2022; 241:113778. [PMID: 36068737 DOI: 10.1016/j.ecoenv.2022.113778] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 05/29/2022] [Accepted: 06/14/2022] [Indexed: 06/15/2023]
Abstract
Organophosphate flame retardants (OPFRs) are alternatives to brominated flame retardants (BFRs) and have recently gained wide acceptance in various materials. For the treatment and prevention of diseases, it is also important to clarify the relationship between OPFRs and tumors, despite the fact that OPFRs are less toxic than BFRs. This research used the TCGA and CTD databases for transcriptome profiling and identifying OPFRs-related genes. GO and KEGG analyses suggested that OPFRs may be closely related to colorectal cancer (CRC), and genes correlated with OPFRs were significantly and differently expressed between tumor and normal group. Further, OPFRs-related genes were associated with a good prognosis in CRC patients. The deeper research demonstrated that one of the OPFRs-triphenyl phosphate could significantly increased the viability and proliferation of CRC cell lines compared with the control group. In addition, Our research also found that melatonin at 50 μM could significantly impact CRC cell proliferation and migration ability induced by TPP.
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Affiliation(s)
- Zhongshi Hong
- Department of General Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Yachen Li
- Medical Department of the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Xian Deng
- Department of General Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Mingliang Chen
- Department of General Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Jianpeng Pan
- Department of General Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Zhichuan Chen
- Department of General Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Xu Zhang
- Nanjing Medical University, Nanjing 210029, China
| | - Chunxiao Wang
- Department of General Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China
| | - Chengzhi Qiu
- Department of General Surgery, the Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian, China.
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