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Avram L, Crișan D, Moldovan RC, Bogos LG, Iuga CA, Andraș D, Crișan S, Bodolea C, Nemeş A, Donca V. Metabolomic Exploration of Colorectal Cancer Through Amino Acids and Acylcarnitines Profiling of Serum Samples. Cancers (Basel) 2025; 17:427. [PMID: 39941796 PMCID: PMC11816151 DOI: 10.3390/cancers17030427] [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: 12/17/2024] [Revised: 01/17/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
BACKGROUND/OBJECTIVES Colorectal cancer (CRC) represents one of the most prevalent forms of cancer, with high mortality rates. The aim of this study was to observe and understand the metabolic changes in CRC through targeted metabolomics. METHODS Samples collected from 58 CRC patients and 35 healthy individuals have been analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), targeting two classes of metabolites: amino acids and acylcarnitines. RESULTS Statistical analysis revealed 26 significantly modified (p-value < 0.01; |FC| > 1.2) metabolites in CRC patients compared to the control group and 22 between colon cancer and control, whereas 8 metabolites differed only significantly between rectal cancer and healthy patients. Some of these significantly modified metabolites characterize cancer-specific adaptations, such as increased energy demand, increased tumor invasiveness, capabilities to promote amino acid synthesis, and tumor resistance against acute immune response. Moreover, receiver operator characteristic (ROC) analysis revealed that a set of two acylcarnitines (C6DC and C4-OH) can differentiate between CRC patients and healthy individuals with a high degree of confidence (AUC 0.837). CONCLUSIONS By implementing a metabolomics approach targeting amino acids and acylcarnitines, several metabolic alterations induced by CRC have been highlighted. Even though these modifications are not specific enough to act as disease markers, they might prove useful for evaluating patient status.
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Affiliation(s)
- Lucreția Avram
- Geriatrics—Gerontology, Department 5—Medical Specialties, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (L.A.); (V.D.)
| | - Dana Crișan
- Department of Internal Medicine, 5th Medical Clinic, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (D.C.); (S.C.)
| | - Radu-Cristian Moldovan
- Department of Personalized Medicine and Rare Diseases, Institute of Biomedical Research—MedFuture, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (L.-G.B.); (C.-A.I.)
| | - Luisa-Gabriela Bogos
- Department of Personalized Medicine and Rare Diseases, Institute of Biomedical Research—MedFuture, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (L.-G.B.); (C.-A.I.)
| | - Cristina-Adela Iuga
- Department of Personalized Medicine and Rare Diseases, Institute of Biomedical Research—MedFuture, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (L.-G.B.); (C.-A.I.)
- Department of Pharmaceutical Analysis, Faculty of Pharmacy, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania
| | - David Andraș
- 1st Surgical Clinic, Department of General Surgery, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400012 Cluj Napoca, Romania;
| | - Sorin Crișan
- Department of Internal Medicine, 5th Medical Clinic, Faculty of Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (D.C.); (S.C.)
| | - Constantin Bodolea
- Intensive Care Unit Department, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (C.B.); (A.N.)
| | - Andrada Nemeş
- Intensive Care Unit Department, “Iuliu Haţieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania; (C.B.); (A.N.)
| | - Valer Donca
- Geriatrics—Gerontology, Department 5—Medical Specialties, Faculty of Medicine, “Iuliu Haţieganu” University of Medicine and Pharmacy Cluj-Napoca, 400012 Cluj-Napoca, Romania; (L.A.); (V.D.)
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Saha S, Ghosh S, Ghosh S, Nandi S, Nayak A. Unraveling the complexities of colorectal cancer and its promising therapies - An updated review. Int Immunopharmacol 2024; 143:113325. [PMID: 39405944 DOI: 10.1016/j.intimp.2024.113325] [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: 05/04/2024] [Revised: 10/01/2024] [Accepted: 10/02/2024] [Indexed: 10/30/2024]
Abstract
Colorectal cancer (CRC) continues to be a global health concern, necessitating further research into its complex biology and innovative treatment approaches. The etiology, pathogenesis, diagnosis, and treatment of colorectal cancer are summarized in this thorough review along with recent developments. The multifactorial nature of colorectal cancer is examined, including genetic predispositions, environmental factors, and lifestyle decisions. The focus is on deciphering the complex interactions between signaling pathways such as Wnt/β-catenin, MAPK, TGF-β as well as PI3K/AKT that participate in the onset, growth, and metastasis of CRC. There is a discussion of various diagnostic modalities that span from traditional colonoscopy to sophisticated molecular techniques like liquid biopsy and radiomics, emphasizing their functions in early identification, prognostication, and treatment stratification. The potential of artificial intelligence as well as machine learning algorithms in improving accuracy as well as efficiency in colorectal cancer diagnosis and management is also explored. Regarding therapy, the review provides a thorough overview of well-known treatments like radiation, chemotherapy, and surgery as well as delves into the newly-emerging areas of targeted therapies as well as immunotherapies. Immune checkpoint inhibitors as well as other molecularly targeted treatments, such as anti-epidermal growth factor receptor (anti-EGFR) as well as anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies, show promise in improving the prognosis of colorectal cancer patients, in particular, those suffering from metastatic disease. This review focuses on giving readers a thorough understanding of colorectal cancer by considering its complexities, the present status of treatment, and potential future paths for therapeutic interventions. Through unraveling the intricate web of this disease, we can develop a more tailored and effective approach to treating CRC.
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Affiliation(s)
- Sayan Saha
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Shreya Ghosh
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Suman Ghosh
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India
| | - Sumit Nandi
- Department of Pharmacology, Gupta College of Technological Sciences, Asansol, West Bengal 713301, India
| | - Aditi Nayak
- Guru Nanak Institute of Pharmaceutical Science and Technology, 157/F, Nilgunj Rd, Sahid Colony, Panihati, Kolkata, West Bengal 700114, India.
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Ji XL, Xu S, Li XY, Xu JH, Han RS, Guo YJ, Duan LP, Tian ZB. Prognostic prediction models for postoperative patients with stage I to III colorectal cancer based on machine learning. World J Gastrointest Oncol 2024; 16:4597-4613. [PMID: 39678810 PMCID: PMC11577370 DOI: 10.4251/wjgo.v16.i12.4597] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 09/07/2024] [Accepted: 09/14/2024] [Indexed: 11/12/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is characterized by high heterogeneity, aggressiveness, and high morbidity and mortality rates. With machine learning (ML) algorithms, patient, tumor, and treatment features can be used to develop and validate models for predicting survival. In addition, important variables can be screened and different applications can be provided that could serve as vital references when making clinical decisions and potentially improving patient outcomes in clinical settings. AIM To construct prognostic prediction models and screen important variables for patients with stage I to III CRC. METHODS More than 1000 postoperative CRC patients were grouped according to survival time (with cutoff values of 3 years and 5 years) and assigned to training and testing cohorts (7:3). For each 3-category survival time, predictions were made by 4 ML algorithms (all-variable and important variable-only datasets), each of which was validated via 5-fold cross-validation and bootstrap validation. Important variables were screened with multivariable regression methods. Model performance was evaluated and compared before and after variable screening with the area under the curve (AUC). SHapley Additive exPlanations (SHAP) further demonstrated the impact of important variables on model decision-making. Nomograms were constructed for practical model application. RESULTS Our ML models performed well; the model performance before and after important parameter identification was consistent, and variable screening was effective. The highest pre- and postscreening model AUCs 95% confidence intervals in the testing set were 0.87 (0.81-0.92) and 0.89 (0.84-0.93) for overall survival, 0.75 (0.69-0.82) and 0.73 (0.64-0.81) for disease-free survival, 0.95 (0.88-1.00) and 0.88 (0.75-0.97) for recurrence-free survival, and 0.76 (0.47-0.95) and 0.80 (0.53-0.94) for distant metastasis-free survival. Repeated cross-validation and bootstrap validation were performed in both the training and testing datasets. The SHAP values of the important variables were consistent with the clinicopathological characteristics of patients with tumors. The nomograms were created. CONCLUSION We constructed a comprehensive, high-accuracy, important variable-based ML architecture for predicting the 3-category survival times. This architecture could serve as a vital reference for managing CRC patients.
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Affiliation(s)
- Xiao-Lin Ji
- Department of Gastroenterology, Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing 100191, China
| | - Shuo Xu
- Beijing Aerospace Wanyuan Science Technology Co., Ltd., China Academy of Launch Vehicle Technology, Beijing 100176, China
| | - Xiao-Yu Li
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Jin-Huan Xu
- Institute of Automation, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, Shandong Province, China
| | - Rong-Shuang Han
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Ying-Jie Guo
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
| | - Li-Ping Duan
- Department of Gastroenterology, Beijing Key Laboratory for Helicobacter Pylori Infection and Upper Gastrointestinal Diseases, Peking University Third Hospital, Beijing 100191, China
| | - Zi-Bin Tian
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
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Fındık DG, Şahin E, Türelik Ö, Güneri G. Epiplakin expression dynamics during colon carcinogenesis: Correlation with proliferation. BIOMOLECULES & BIOMEDICINE 2024; 25:62-70. [PMID: 39052015 PMCID: PMC11647249 DOI: 10.17305/bb.2024.10981] [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: 07/11/2024] [Revised: 07/23/2024] [Accepted: 07/23/2024] [Indexed: 07/27/2024]
Abstract
Colorectal cancer poses a significant global health challenge, with a considerable proportion arising from colon adenomas. Understanding the molecules involved in the carcinogenesis process is crucial for improving colon cancer diagnosis and prognosis. While research on the role of epiplakin in cancer remains limited compared to other plakin group proteins, comprehending its expression patterns and correlations can offer valuable insights into colon carcinogenesis. In this study, we analyzed 60 tissue samples, including colon adenocarcinomas, tubular adenomas (low malignancy risk group), tubulovillous adenomas (high malignancy risk group), and adjacent normal colon tissues. Classification and grading were reevaluated by histological examination. Immunohistochemistry was performed to assess epiplakin and Ki67 expression. Epiplakin optical density and the Ki67 proliferation index were calculated using ImageJ. Statistical analyses were conducted to evaluate correlations and significance. Epiplakin expression was significantly decreased in colon adenocarcinomas [optical density median 4.04 (95% CI, 3.98 to 4.24)] and tubulovillous adenomas [4.32 (95% CI, 4.08 to 4.32)] compared to normal colon tissues [4.61 (95% CI, 4.50 to 4.67)] and tubular adenomas [4.87 (95% CI, 4.67 to 4.88)] (P < 0.05). Moreover, adenoma groups exhibited higher proliferation indices (P < 0.05), and a positive correlation was found between epiplakin expression and the Ki67 proliferation index (r = 0.317, P < 0.05). Our study highlights the potential significance of epiplakin in colorectal cancer. Decreased epiplakin expression is associated with colon malignancy progression, suggesting its role as a potential marker.
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Affiliation(s)
- Damla Gül Fındık
- Department of Histology and Embryology, Faculty of Medicine, Bilecik Şeyh Edebali University, Bilecik, Türkiye
| | - Erhan Şahin
- Department of Histology and Embryology, Faculty of Medicine, Bilecik Şeyh Edebali University, Bilecik, Türkiye
| | - Özlem Türelik
- Department of Pathology, Faculty of Medicine, Bilecik Şeyh Edebali University, Bilecik, Türkiye
| | - Gürkan Güneri
- Department of General Surgery, Faculty of Medicine, Bilecik Şeyh Edebali University, Bilecik, Türkiye
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Li Y, Xu C, Weng W, Goel A. Combined treatment with Aronia berry extract and oligomeric proanthocyanidins exhibit a synergistic anticancer efficacy through LMNB1-AKT signaling pathways in colorectal cancer. Mol Carcinog 2024; 63:2145-2157. [PMID: 39282961 DOI: 10.1002/mc.23800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 07/22/2024] [Indexed: 10/04/2024]
Abstract
Colorectal cancer (CRC) is one of the most prevalent and highly recurrent malignancies worldwide and currently ranks as the second leading cause of cancer-related deaths. The high degree of morbidity and mortality associated with CRC is primarily attributed to the limited effectiveness of current therapeutic approaches and the emergence of chemoresistance to standard treatment modalities. Recent research indicates that several natural products, including Aronia berry extracts (ABE) and oligomeric proanthocyanidins (OPCs), might offer a safe, cost-effective, and multitargeted adjunctive role to cancer treatment. Herein, we hypothesized a combined treatment with ABE and OPCs could synergistically modulate multiple oncogenic pathways in CRC, thereby enhancing their anticancer activity. We initially conducted a series of in vitro experiments to assess the synergistic anticancer effects of ABE and OPCs on CRC cell lines. We demonstrate that these two compounds exhibited a superior synergistic anticancer potential versus individual treatments in enhancing the ability to inhibit cell viability, suppress colony formation, and induce apoptosis (p < 0.05). Consistent with our in vitro findings, we validated this combinatorial anticancer effect in tumor-derived 3D organoids (PDOs; p < 0.01). Using genome-wide transcriptomic profiling, we identified that a specific gene, LMNB1, associated with the cell apoptosis pathway, was found to play a crucial role in exhibiting anticancer effects with these two products. Furthermore, the combined treatment of ABE and OPCs significantly impacted the expression of key proteins involved in apoptosis, including suppressed expression levels of LMNB1 in CRC cell lines (p < 0.05), which resulted in inhibiting downstream AKT phosphorylation. In conclusion, our study provides novel evidence of the synergistic anticancer effects of ABE and OPCs in CRC cells, partially mediated through the regulation of apoptosis and the oncogene LMNB1 within the AKT signaling pathway. These findings have the potential to better appreciate the anticancer potential of natural products in CRC and help improve treatment outcomes in this malignancy.
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Affiliation(s)
- Yuan Li
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, California, USA
- Department of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, China
| | - Caiming Xu
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, California, USA
- Department of General Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Wenhao Weng
- Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, China
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, California, USA
- City of Hope Comprehensive Cancer Center, Duarte, California, USA
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Ibrar F, Atiq M, Shafqat F, Khan HM. Early onset Colorectal Cancer and its association with its histological subtypes. Pak J Med Sci 2024; 40:2395-2399. [PMID: 39554668 PMCID: PMC11568735 DOI: 10.12669/pjms.40.10.10143] [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: 04/16/2024] [Revised: 05/18/2024] [Accepted: 08/05/2024] [Indexed: 11/19/2024] Open
Abstract
Objective There are different clinicopathological features between early and late onset colorectal cancer. We aimed to characterize the histological features of colorectal cancer (CRC) at different age groups in our institution. Methods Total 232 patients with histologically proven colorectal cancer between ages 13-99 were included. This is retrospective study. Data collected from tumour registry Shifa International Hospital from January 1st 2018 to December 31st 2020. Pearson Chi square test was used for significance of categorical variables. P-values less than 0.05 were considered significant. Results Mean age at diagnosis was 55.49+/-16.43 years. Out of total 232 patients 58.6% were male and 41.3% were females (p value= 0.16). 150 (64.9%) were aged > 50 years and 81 (35.1%) were age < or equal to 50 years (p value = 0.44). Most common histological subtype was adenocarcinoma that was found in 188 (81%) cases. One hundred fifty five (66.8%) patients had Grade-II tumor, 67(28.9%) with Grade-III and 10 (4.3%) with Grade-I tumor. Fifty eight (25%) patients presented with metastatic disease. A significantly higher percentage of patients with signet ring cell cancer presented with a high-grade tumor when compared with patients with adenocarcinoma and mucinous carcinoma (93.7% vs 21.8%, p-value- <0.001%; 93.7% vs 39.2%, p-value <0.001). A significantly higher percentage of patients with mucinous adenocarcinoma and signet ring cell carcinoma presented at age less than 50 as compared to those with adenocarcinoma (60.7%, 56.2% and 30.8% respectively; p-value <0.05). Conclusion This study signifies that mucinous and signet ring cell type CRC present at an early age and with a higher proportion of patients with high tumour grade. Early diagnosis is key to help improve outcomes in these patients.
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Affiliation(s)
- Fatima Ibrar
- Fatima Ibrar, Departments of Gastroenterology Hepatology, Surgery and Pathology Shifa International Hospital, Islamabad, Pakistan
| | - Muslim Atiq
- Muslim Atiq, Departments of Gastroenterology Hepatology, Surgery and Pathology Shifa International Hospital, Islamabad, Pakistan
| | - Farzana Shafqat
- Farzana Shafqat, Departments of Gastroenterology Hepatology, Surgery and Pathology Shifa International Hospital, Islamabad, Pakistan
| | - Hadi Mohammad Khan
- Hadi Mohammad Khan, Departments of Gastroenterology Hepatology, Surgery and Pathology Shifa International Hospital, Islamabad, Pakistan
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El Bali M, Mesmoudi M, Essayah A, Arbai K, Ghailani Nourouti N, Barakat A, Sellal N, Bennani Mechita M. Epidemiological and anatomopathological profile of colorectal cancer in Northern Morocco between 2017 and 2019. Arab J Gastroenterol 2024; 25:338-344. [PMID: 39505674 DOI: 10.1016/j.ajg.2024.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 10/03/2024] [Accepted: 10/15/2024] [Indexed: 11/08/2024]
Abstract
BACKGROUND AND STUDY AIMS Colorectal cancer (CRC) is the third most common type of cancer worldwide and the second leading cause of cancer-related death. CRC represents a major public health problem in many countries, and its incidence is increasing worldwide. In Morocco, CRC is the third most common cancer. However, epidemiological data on CRC in Morocco, especially in the north, are very limited. This study aimed to describe the epidemiological and clinicopathological characteristics of CRC in northern Morocco. PATIENTS AND METHODS This retrospective study was conducted at the Ahmed Ben Zayed Al Nahyan Regional Oncology Center of Tangier between April 2017 and December 2019. Data were collected from the medical records of confirmed CRC patients and analyzed using SPSS computer software version 23. RESULTS CRC was detected in 142 patients, accounting for 13.0 % of all cancers identified during the study period in the center. The sex ratio (male/female) of all patients was 1.1. The mean age was 58 years, and the most affected group was 60-69 years old (29.0 %). The rectum was the most common anatomical site (44.0 %) compared to the left and right colon. Histologically, adenocarcinomas were the most common type (91.3 %), half of the tumors were moderately differentiated, and only 4.9 % of the patients presented with poorly differentiated tumors. At diagnosis, 83.0 % of patients were already in advanced stages (stage III, or IV), including 40.3 % presenting with metastatic disease. The liver (64.8 %) was the most affected site by metastasis in our series. Relapse was observed in 11.9 % of patients. CONCLUSION Our results showed a younger age at diagnosis and a higher incidence of cancer at the rectal site compared to the Western literature, as well as a high frequency of patients who presented with late-stage disease and other characteristics. However, larger multicenter studies are still needed to confirm our results.
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Affiliation(s)
- Mouade El Bali
- Intelligent Automation & BioMed Genomics Laboratory, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University-Tetouan, Morocco.
| | - Mohamed Mesmoudi
- Ahmed Ben Zayed Al Nahyan Center of Cancer Treatment, Tangier, Morocco
| | - Amale Essayah
- Intelligent Automation & BioMed Genomics Laboratory, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University-Tetouan, Morocco
| | - Kenza Arbai
- Intelligent Automation & BioMed Genomics Laboratory, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University-Tetouan, Morocco
| | - Naima Ghailani Nourouti
- Intelligent Automation & BioMed Genomics Laboratory, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University-Tetouan, Morocco
| | - Amina Barakat
- Intelligent Automation & BioMed Genomics Laboratory, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University-Tetouan, Morocco
| | - Nabila Sellal
- Ahmed Ben Zayed Al Nahyan Center of Cancer Treatment, Tangier, Morocco
| | - Mohcine Bennani Mechita
- Intelligent Automation & BioMed Genomics Laboratory, Faculty of Sciences and Techniques of Tangier, Abdelmalek Essaadi University-Tetouan, Morocco
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Hu ZX, Li Y, Yang X, Li YX, He YY, Niu XH, Nie TT, Guo XF, Yuan ZL. Constructing a nomogram to predict overall survival of colon cancer based on computed tomography characteristics and clinicopathological factors. World J Gastrointest Oncol 2024; 16:4104-4114. [DOI: 10.4251/wjgo.v16.i10.4104] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 08/18/2024] [Accepted: 09/06/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND The colon cancer prognosis is influenced by multiple factors, including clinical, pathological, and non-biological factors. However, only a few studies have focused on computed tomography (CT) imaging features. Therefore, this study aims to predict the prognosis of patients with colon cancer by combining CT imaging features with clinical and pathological characteristics, and establishes a nomogram to provide critical guidance for the individualized treatment.
AIM To establish and validate a nomogram to predict the overall survival (OS) of patients with colon cancer.
METHODS A retrospective analysis was conducted on the survival data of 249 patients with colon cancer confirmed by surgical pathology between January 2017 and December 2021. The patients were randomly divided into training and testing groups at a 1:1 ratio. Univariate and multivariate logistic regression analyses were performed to identify the independent risk factors associated with OS, and a nomogram model was constructed for the training group. Survival curves were calculated using the Kaplan–Meier method. The concordance index (C-index) and calibration curve were used to evaluate the nomogram model in the training and testing groups.
RESULTS Multivariate logistic regression analysis revealed that lymph node metastasis on CT, perineural invasion, and tumor classification were independent prognostic factors. A nomogram incorporating these variables was constructed, and the C-index of the training and testing groups was 0.804 and 0.692, respectively. The calibration curves demonstrated good consistency between the actual values and predicted probabilities of OS.
CONCLUSION A nomogram combining CT imaging characteristics and clinicopathological factors exhibited good discrimination and reliability. It can aid clinicians in risk stratification and postoperative monitoring and provide important guidance for the individualized treatment of patients with colon cancer.
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Affiliation(s)
- Zhe-Xing Hu
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Yin Li
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Xuan Yang
- Department of Radiology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China
| | - Yu-Xia Li
- College of Informatics, Huazhong Agriculture University, Wuhan 430070, Hubei Province, China
| | - Yao-Yao He
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Xiao-Hui Niu
- College of Informatics, Huazhong Agriculture University, Wuhan 430070, Hubei Province, China
| | - Ting-Ting Nie
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Xiao-Fang Guo
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
| | - Zi-Long Yuan
- Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430079, Hubei Province, China
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Krzywoń L, Lazaris A, Petrillo SK, Zlotnik O, Gao ZH, Metrakos P. Histopathological Growth Patterns Determine the Outcomes of Colorectal Cancer Liver Metastasis Following Liver Resection. Cancers (Basel) 2024; 16:3148. [PMID: 39335120 PMCID: PMC11430747 DOI: 10.3390/cancers16183148] [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: 07/23/2024] [Revised: 08/14/2024] [Accepted: 08/17/2024] [Indexed: 09/30/2024] Open
Abstract
INTRODUCTION Colorectal cancer liver metastasis (CRCLM) remains a lethal diagnosis, with an overall 5-year survival rate of 5-10%. Two distinct histopathological growth patterns (HGPs) of CRCLM are known to have significantly differing rates of patient survival and response to treatment. We set out to review the results of 275 patients who underwent liver resection for CRCLM at the McGill University Health Center (MUHC) and analyze their clinical outcome, mutational burden, and pattern of cancer progression in light of their HGPs, and to consider their potential effect on surgical decision making. METHODS We performed a retrospective multivariate analysis on clinical data from patients with CRCLM (n = 275) who underwent liver resection at the McGill University Health Center (MUHC). All tumors were scored using international consensus guidelines by pathologists trained in HGP scoring. RESULTS A total of 109 patients (42.2%) were classified as desmoplastic and angiogenic, whereas 149 patients (57.7%) were non-desmoplastic and vessel co-opting. The 5-year survival rates for angiogenic patients compared with vessel co-opting patients were 47.1% and 13%, respectively (p < 0.0001). Multivariate analysis showed patients with vessel co-opting CRCLM had a higher incidence of extrahepatic metastatic disease (p = 0.0215) compared with angiogenic CRCLM. Additionally, KRAS mutation status was a marker of increased likelihood of disease recurrence (p = 0.0434), as was increased number of liver tumors (p = 0.0071) and multiple sites of extrahepatic metastatic disease (p < 0.0001). CONCLUSIONS Multivariate analysis identified key clinical prognostic and molecular features correlating with the two HGPs. Determining liver tumor HGPs is essential for patient prognostication and treatment optimization.
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Affiliation(s)
- Lucyna Krzywoń
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
- Department of Experimental Surgery, McGill University, 1650 Cedar Ave., Room A7.117, Montreal, QC H4A 3J1, Canada
| | - Anthoula Lazaris
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
| | - Stephanie K Petrillo
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
| | - Oran Zlotnik
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
- Department of Experimental Surgery, McGill University, 1650 Cedar Ave., Room A7.117, Montreal, QC H4A 3J1, Canada
| | - Zu-Hua Gao
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
- Department of Pathology and Labaratory Medicine, University of British Columbia, Rm. G227-2211 Wesbrook Mall, Vancouver, BC V6T 2B5, Canada
- McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada
| | - Peter Metrakos
- Cancer Research Program, Research Institute of McGill University Health Center Glen Site, McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd Room E02.6218, Montreal, QC H4A 3J1, Canada
- McGill University Health Center, Royal Victoria Hospital-Glen Site, 1001 Decarie Blvd, Montreal, QC H4A 3J1, Canada
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10
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Otálora-Otálora BA, Payán-Gómez C, López-Rivera JJ, Pedroza-Aconcha NB, Aristizábal-Guzmán C, Isaza-Ruget MA, Álvarez-Moreno CA. Global transcriptomic network analysis of the crosstalk between microbiota and cancer-related cells in the oral-gut-lung axis. Front Cell Infect Microbiol 2024; 14:1425388. [PMID: 39228892 PMCID: PMC11368877 DOI: 10.3389/fcimb.2024.1425388] [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: 04/29/2024] [Accepted: 07/15/2024] [Indexed: 09/05/2024] Open
Abstract
Background The diagnosis and treatment of lung, colon, and gastric cancer through the histologic characteristics and genomic biomarkers have not had a strong impact on the mortality rates of the top three global causes of death by cancer. Methods Twenty-five transcriptomic analyses (10 lung cancer, 10 gastric cancer, and 5 colon cancer datasets) followed our own bioinformatic pipeline based on the utilization of specialized libraries from the R language and DAVID´s gene enrichment analyses to identify a regulatory metafirm network of transcription factors and target genes common in every type of cancer, with experimental evidence that supports its relationship with the unlocking of cell phenotypic plasticity for the acquisition of the hallmarks of cancer during the tumoral process. The network's regulatory functional and signaling pathways might depend on the constant crosstalk with the microbiome network established in the oral-gut-lung axis. Results The global transcriptomic network analysis highlighted the impact of transcription factors (SOX4, TCF3, TEAD4, ETV4, and FOXM1) that might be related to stem cell programming and cancer progression through the regulation of the expression of genes, such as cancer-cell membrane receptors, that interact with several microorganisms, including human T-cell leukemia virus 1 (HTLV-1), the human papilloma virus (HPV), the Epstein-Barr virus (EBV), and SARS-CoV-2. These interactions can trigger the MAPK, non-canonical WNT, and IFN signaling pathways, which regulate key transcription factor overexpression during the establishment and progression of lung, colon, and gastric cancer, respectively, along with the formation of the microbiome network. Conclusion The global transcriptomic network analysis highlights the important interaction between key transcription factors in lung, colon, and gastric cancer, which regulates the expression of cancer-cell membrane receptors for the interaction with the microbiome network during the tumorigenic process.
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Affiliation(s)
| | - César Payán-Gómez
- Dirección Académica, Universidad Nacional de Colombia, Sede de La Paz, La Paz, Colombia
| | - Juan Javier López-Rivera
- Grupo de Investigación INPAC, Specialized Laboratory, Clinica Universitaria Colombia, Clínica Colsanitas S.A., Bogotá, Colombia
| | | | - Claudia Aristizábal-Guzmán
- Grupo de Investigación INPAC, Unidad de Investigación, Fundación Universitaria Sanitas, Bogotá, Colombia
| | - Mario Arturo Isaza-Ruget
- Keralty, Sanitas International Organization, Grupo de Investigación INPAC, Fundación Universitaria Sanitas, Bogotá, Colombia
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11
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Zhang J, Wang Y, Hou S, Chi X, Ding D, Xue M, Zhang M, Wang J, Shuai J, Sun H, Gao Q, Kang C. Overexpression of ZNF169 promotes the growth and proliferation of colorectal cancer cells via the upregulation of ANKZF1. Oncol Rep 2024; 51:82. [PMID: 38666541 PMCID: PMC11063753 DOI: 10.3892/or.2024.8741] [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] [Accepted: 04/05/2024] [Indexed: 05/01/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies worldwide. The 5‑year survival rate of patients diagnosed with the early stages of the disease is markedly higher than that of patients in the advanced stages. Therefore, identifying novel biomarkers and drug targets for CRC is critical for clinical practice. Zinc finger protein 169 (ZNF169) is a crucial transcription factor, and its role in CRC remains to be explored. The present study aimed to investigate the clinical relevance, function and underlying mechanisms of ZNF169 in CRC growth and proliferation. The Cancer Genome Atlas (TCGA) database was utilized to analyze the clinical relevance of ZNF169 in patients with CRC. Immunohistochemical staining was performed on tissue samples from patients with CRC to detect the expression of ZNF169. The HCT‑116, HT‑29 and RKO cell lines were employed for in vitro experiments. The overexpression and knockdown of ZNF169 were achieved by transfecting the cells with lentivirus and small interfering RNAs, respectively. Cell Counting Kit‑8, colony formation and EdU staining assays were applied to investigate the function of ZNF169 in CRC cells. Dual luciferase activity and chromatin immunoprecipitation (ChIP)‑quantitative PCR (qPCR) assays were performed to identify the regulatory effects of ZNF169 on the ankyrin repeat and zinc‑finger domain‑containing 1 (ANKZF1; also known as ZNF744) gene. Reverse transcription‑quantitative PCR and western blot analysis were performed to measure mRNA and protein expression, respectively. The analysis of TCGA data revealed a positive correlation between ZNF169 and ANKZF1, with the overexpression of ANKZF1 being associated with a poor prognosis of patients with CRC. The experimental results demonstrated that ZNF169 was expression upregulated in CRC tissue compared with that in normal colon tissue. Gain‑of‑function and loss‑of‑function experiments revealed that ZNF169 enhanced the intensity of EdU staining, promoting the growth and proliferation of CRC cells. Furthermore, the overexpression of ZNF169 potentiated the transcriptional activity of the ANKZF1 gene, while the knockdown of ZNF169 produced the opposite results. ChIP‑qPCR confirmed the interaction between ZNF169 and the promoter sequence of ANKZF1. Rescue experiments revealed that ZNF169 accelerated CRC cell growth and proliferation through the upregulation of ANKZF1. Furthermore, there was a positive correlation identified between ZNF169 and ANKZF1, and upregulation of ANKZF1 expression was associated with the poor prognosis of patients with CRC. On the whole, the present study demonstrates that ZNF169 contributes to CRC malignancy by potentiating the expression of ANKZF1. Thus, the regulation of ZNF169 and/or ANKZF1 expression may represent a viable strategy for the treatment patients with CRC with a high expression of ZNF169.
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Affiliation(s)
- Jie Zhang
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Ye Wang
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Shiyang Hou
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Xiaoqian Chi
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Danyang Ding
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Mei Xue
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Mengqiao Zhang
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Jing Wang
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Junfang Shuai
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Haiying Sun
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Qiang Gao
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Chunbo Kang
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
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12
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Nuytens F, Drubay V, Eveno C, Renaud F, Piessen G. Systematic review of risk factors, prognosis, and management of colorectal signet-ring cell carcinoma. World J Gastrointest Oncol 2024; 16:2141-2158. [PMID: 38764832 PMCID: PMC11099453 DOI: 10.4251/wjgo.v16.i5.2141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 01/27/2024] [Accepted: 03/19/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND Colorectal signet-ring cell carcinoma (CSRCC) is a rare clinical entity which accounts for approximately 1% of all colorectal cancers. Although multiple studies concerning this specific topic have been published in the past decades, the pathogenesis, associated risk factors, and potential implications on treatment are still poorly understood. Besides the low incidence, historically confusing histological criteria have resulted in confusing data. Nevertheless, the rising incidence of CSRCC along with relatively young age at presentation and associated dismal prognosis, highlight the actual interest to synthesize the known literature regarding CSRCC. AIM To provide an updated overview of risk factors, prognosis, and management of CSRCC. METHODS A literature search in the MEDLINE/PubMed database was conducted with the following search terms used: 'Signet ring cell carcinoma' and 'colorectal'. Studies in English language, published after January 1980, were included. Studies included in the qualitative synthesis were evaluated for content concerning epidemiology, risk factors, and clinical, diagnostic, histological, and molecular features, as well as metastatic pattern and therapeutic management. If possible, presented data was extracted in order to present a more detailed overview of the literature. RESULTS In total, 67 articles were included for qualitative analysis, of which 54 were eligible for detailed data extraction. CSRCC has a reported incidence between 0.1%-2.4% and frequently presents with advanced disease stage at the time of diagnosis. CSRCC is associated with an impaired overall survival (5-year OS: 0%-46%) and a worse stage-corrected outcome compared to mucinous and not otherwise specified adenocarcinoma. The systematic use of exploratory laparoscopy to determine the presence of peritoneal metastases has been advised. Surgery is the mainstay of treatment, although the rates of curative resection in CSRCC (21%-82%) are lower compared to those in other histological types. In case of peritoneal metastasis, cytoreductive surgery with hyperthermic intraperitoneal chemotherapy should only be proposed in selected patients. CONCLUSION CSRCC is a rare clinical entity most often characterized by young age and advanced disease at presentation. As such, diagnostic modalities and therapeutic approach should be tailored accordingly.
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Affiliation(s)
- Frederiek Nuytens
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- Department of Digestive and Hepatobiliary/Pancreatic Surgery, AZ Groeninge, Kortrijk 8500, Belgium
| | - Vincent Drubay
- Cambrai Hospital Center and Sainte Marie, Group of Hospitals of The Catholic Institute of Lille, Cambrai 59400, France
| | - Clarisse Eveno
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
| | - Florence Renaud
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
| | - Guillaume Piessen
- Department of Digestive and Oncological Surgery, University Lille, Claude Huriez University Hospital, Lille 59000, France
- CNRS, Inserm, UMR9020-U1277-CANTHER-Cancer, University Lille, CHU Lille, Lille 59000, France
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13
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Saadi S, Aarab M, Tabyaoui I, Jouti NT. Circulating tumor cells in colorectal cancer - a review of detection methods and clinical relevance. Contemp Oncol (Pozn) 2023; 27:123-131. [PMID: 38239860 PMCID: PMC10793619 DOI: 10.5114/wo.2023.133740] [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: 06/21/2023] [Accepted: 09/08/2023] [Indexed: 01/22/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer; it is one of the leading malignancies contributing to cancer mortality. Colorectal cancer is the third most diagnosed cancer in men and the second in women worldwide. Diagnosis of CRC depends on several clinical features such as age, primary site, tumor-node-metastasis stage, genetic parameters and the presence or absence of metastasis. The latter is a phenomenon that is induced by the shedding of tumor cells in the blood circulation by the primary tumor. Such cells are known as circulating tumor cells (CTCs). The detection of CTCs is quite challenging due to their scarceness; thus it requires their enrichment and characterization. Studying the utility of CTCs in the diagnosis of CRC has been the aim of several studies; they demonstrated that ≥ 3 CTCs in 7.5 ml of blood is correlated with a worse prognosis and short progression-free and overall survival. Circulating tumor cells have also been monitored to study treatment response and predict future relapses. The present review aims to bring to light the different techniques used to detect and characterize these malignant cells in the peripheral blood of cancer patients as well as the clinical relevance of CTCs in CRC patients.
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Affiliation(s)
- Salma Saadi
- Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology – Faculty of Medicine and Pharmacy of Casablanca Hassan II University, Casablanca, Morocco
| | - Meryem Aarab
- Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology – Faculty of Medicine and Pharmacy of Casablanca Hassan II University, Casablanca, Morocco
| | - Imane Tabyaoui
- Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology – Faculty of Medicine and Pharmacy of Casablanca Hassan II University, Casablanca, Morocco
| | - Nadia Tahiri Jouti
- Laboratory of Cellular and Molecular Inflammatory, Degenerative and Oncologic Pathophysiology – Faculty of Medicine and Pharmacy of Casablanca Hassan II University, Casablanca, Morocco
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Kang C, Zhang J, Xue M, Li X, Ding D, Wang Y, Jiang S, Chu FF, Gao Q, Zhang M. Metabolomics analyses of cancer tissue from patients with colorectal cancer. Mol Med Rep 2023; 28:219. [PMID: 37772396 PMCID: PMC10568249 DOI: 10.3892/mmr.2023.13106] [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: 02/27/2023] [Accepted: 07/31/2023] [Indexed: 09/30/2023] Open
Abstract
The alteration of metabolism is essential for the initiation and progression of numerous types of cancer, including colorectal cancer (CRC). Metabolomics has been used to study CRC. At present, the reprogramming of the metabolism in CRC remains to be fully elucidated. In the present study, comprehensive untargeted metabolomics analysis was performed on the paired CRC tissues and adjacent normal tissues from patients with CRC (n=35) using ultra‑high‑performance liquid chromatography‑mass spectrometry. Subsequently, bioinformatic analysis was performed on the differentially expressed metabolites. The changes in these differential metabolites were compared among groups of patients based on sex, anatomical tumor location, grade of tumor differentiation and stage of disease. A total of 927 metabolites were detected in the tissue samples, and 24 metabolites in the CRC tissue were significantly different compared with the adjacent normal tissue. The present study revealed that the levels of three amino acid metabolites were increased in the CRC tissue, specifically, N‑α‑acetyl‑ε‑(2‑propenal)‑Lys, cyclo(Glu‑Glu) and cyclo(Phe‑Glu). The metabolites with decreased levels in the CRC tissue included quinaldic acid (also referred to as quinoline‑2‑carboxilic acid), 17α‑ and 17β‑estradiol, which are associated with tumor suppression activities, as well as other metabolites such as, anhydro‑β‑glucose, Asp‑Arg, lysophosphatidylcholine, lysophosphatidylethanolamine (lysoPE), lysophosphatidylinositol, carnitine, 5'‑deoxy‑5'‑(methylthio) adenosine, 2'‑deoxyinosine‑5'‑monophosphate and thiamine monophosphate. There was no difference in the levels of the differential metabolites between male and female patients. The differentiation of CRC also showed no impact on the levels of the differential metabolites. The levels of lysoPE were increased in the right side of the colon compared with the left side of the colon and rectum. Analysis of the different tumor stages indicated that 2‑aminobenzenesulfonic acid, P‑sulfanilic acid and quinoline‑4‑carboxylic acid were decreased in stage I CRC tissue compared with stage II, III and IV CRC tissue. The levels of N‑α‑acetyl‑ε‑(2‑propenal)‑Lys, methylcysteine and 5'‑deoxy‑5'‑(methylthio) adenosine varied at different stages of tumorigenesis. These differential metabolites were implicated in multiple metabolism pathways, including carbohydrate, amino acid, lipid, nucleotide and hormone. In conclusion, the present study demonstrated that CRC tumors had altered metabolites compared with normal tissue. The data from the metabolic profile of CRC tissues in the present study provided supportive evidence to understand tumorigenesis.
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Affiliation(s)
- Chunbo Kang
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Jie Zhang
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Mei Xue
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Xiaowei Li
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Danyang Ding
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Ye Wang
- Department of Surgery, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Shujing Jiang
- Department of Acute Medicine, Queen Elizabeth Hospital, London SE18 4QH, UK
| | - Fong-Fong Chu
- Department of Cancer Genetics and Epigenetics, Beckman Research Institute of The City of Hope, Duarte, CA 91010, USA
| | - Qiang Gao
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
| | - Mengqiao Zhang
- Department of Gastroenterology and Hepatology, Center of Gastrointestinal Rehabilitation, Beijing Rehabilitation Hospital, Capital Medical University, Beijing 100144, P.R. China
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Saoudi González N, Salvà F, Ros J, Baraibar I, Rodríguez-Castells M, García A, Alcaráz A, Vega S, Bueno S, Tabernero J, Elez E. Unravelling the Complexity of Colorectal Cancer: Heterogeneity, Clonal Evolution, and Clinical Implications. Cancers (Basel) 2023; 15:4020. [PMID: 37627048 PMCID: PMC10452468 DOI: 10.3390/cancers15164020] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/01/2023] [Accepted: 08/02/2023] [Indexed: 08/27/2023] Open
Abstract
Colorectal cancer (CRC) is a global health concern and a leading cause of death worldwide. The disease's course and response to treatment are significantly influenced by its heterogeneity, both within a single lesion and between primary and metastatic sites. Biomarkers, such as mutations in KRAS, NRAS, and BRAF, provide valuable guidance for treatment decisions in patients with metastatic CRC. While high concordance exists between mutational status in primary and metastatic lesions, some heterogeneity may be present. Circulating tumor DNA (ctDNA) analysis has proven invaluable in identifying genetic heterogeneity and predicting prognosis in RAS-mutated metastatic CRC patients. Tumor heterogeneity can arise from genetic and non-genetic factors, affecting tumor development and response to therapy. To comprehend and address clonal evolution and intratumoral heterogeneity, comprehensive genomic studies employing techniques such as next-generation sequencing and computational analysis are essential. Liquid biopsy, notably through analysis of ctDNA, enables real-time clonal evolution and treatment response monitoring. However, challenges remain in standardizing procedures and accurately characterizing tumor subpopulations. Various models elucidate the origin of CRC heterogeneity, highlighting the intricate molecular pathways involved. This review focuses on intrapatient cancer heterogeneity and genetic clonal evolution in metastatic CRC, with an emphasis on clinical applications.
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Affiliation(s)
- Nadia Saoudi González
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Francesc Salvà
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Javier Ros
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Iosune Baraibar
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Marta Rodríguez-Castells
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Ariadna García
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
| | - Adriana Alcaráz
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Sharela Vega
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Sergio Bueno
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Josep Tabernero
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
| | - Elena Elez
- Vall d’Hebron Institute of Oncology, 08035 Barcelona, Spain; (N.S.G.)
- Oncology Department, Vall d’Hebron Hospital, 08035 Barcelona, Spain
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Enblad M, Egerszegi PP, Birgisson H, Sjöblom T, Glimelius B, Folkesson J. Signet Ring Cell Colorectal and Appendiceal Cancer: A Small Signet Ring Cell Component Is Also Associated with Poor Outcome. Cancers (Basel) 2023; 15:cancers15092497. [PMID: 37173961 PMCID: PMC10177230 DOI: 10.3390/cancers15092497] [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: 03/09/2023] [Revised: 04/24/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
BACKGROUND Colorectal signet ring cell (SRC) carcinoma with ≥50% SRCs (SRC ≥ 50) has a poor prognosis, but the prognostic role of SRCs < 50% (SRC < 50) is unclear. The aim of this study was to provide a clinicopathological characterization of SRC colorectal and appendiceal tumours and analyse the importance of the SRC component size. METHODS All patients in the Swedish Colorectal Cancer Registry diagnosed with colorectal or appendiceal cancer in 2009-2020 at Uppsala University Hospital, Sweden, were included. The SRCs were verified, and the components estimated by a gastrointestinal pathologist. RESULTS Of the 2229 colorectal cancers, 51 (2.3%) had SRCs, with a median component size of 30% (interquartile range of 12.5-40) and 10 (0.45%) had SRC ≥ 50. The SRC tumours were primarily localized in the right colon (59%) and appendix (16%). No patients with SRCs had stage I disease, and 26 (51%) had stage IV, of whom, 18 (69%) had peritoneal metastases. The SRC tumours were often high grade with perineural and vascular invasion. The 5-year overall survival (OS) rate for patients with SRC ≥ 50 were 20% (95% confidence interval (CI) 6-70), for SRC < 50, 39% (95% CI 24-61); and for non-SRCs, 55% (95% CI 55-60). Among the patients with SRC < 50 and <50% extracellular mucin, the 5-year OS was 34% (95% CI 19-61), while those with ≥50% extracellular mucin had an OS of 50% (95% CI 25-99). The 5-year recurrence-free survival rates were 51% (95% CI 13-83) for patients with SRC tumours, as compared to 83% (95% CI 77-89) and 81% (95% CI 79-84) for mucinous and non-mucinous adenocarcinoma, respectively. CONCLUSIONS The presence of SRCs was strongly associated with aggressive clinicopathological features, peritoneal metastases, and poor prognosis, also when they make up <50% of a tumour.
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Affiliation(s)
- Malin Enblad
- Department of Surgical Sciences, Colorectal Surgery, Uppsala University, 751 85 Uppsala, Sweden
| | - Péter Pál Egerszegi
- Department of Immunology, Genetics and Pathology, Clinical Pathology, Uppsala University, 751 08 Uppsala, Sweden
| | - Helgi Birgisson
- Department of Surgical Sciences, Colorectal Surgery, Uppsala University, 751 85 Uppsala, Sweden
| | - Tobias Sjöblom
- Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology, Uppsala University, 751 85 Uppsala, Sweden
| | - Bengt Glimelius
- Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology, Uppsala University, 751 85 Uppsala, Sweden
| | - Joakim Folkesson
- Department of Surgical Sciences, Colorectal Surgery, Uppsala University, 751 85 Uppsala, Sweden
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17
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Wang R, Lian J, Wang X, Pang X, Xu B, Tang S, Shao J, Lu H. Survival rate of colorectal cancer in China: A systematic review and meta-analysis. Front Oncol 2023; 13:1033154. [PMID: 36937415 PMCID: PMC10020492 DOI: 10.3389/fonc.2023.1033154] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 02/20/2023] [Indexed: 03/06/2023] Open
Abstract
Background This study aims to comprehensively summarize the colorectal survival rate in China. Method: In PubMed and Web of Science, keywords such as "colorectal cancer", "survival" and "China" were used to search literatures in the past 10 years. Random effect models were selected to summarize 1-year, 3-year, and 5-year survival rates, and meta-regression and subgroup analyses were performed on the included studies. Results A total of 16 retrospective and prospective studies providing survival rates for colorectal cancer in China were included. The 1-year, 3-year, and 5-year survival rates of colorectal cancer in China were 0.79, 0.72 and 0.62, respectively. In the included studies, the 5-year survival rates of stage I (5474 cases), stage II (9215 cases), stage III (8048 cases), and stage IV (4199 cases) colorectal cancer patients were 0.85, 0.81, 0.57 and 0.30, respectively. Among them, the 5-year survival rates of colorectal cancer were 0.82, 0.76, 0.71, 0.67, 0.66, 0.65 and 0.63 in Tianjin, Beijing, Guangdong, Shandong, Liaoning, Zhejiang and Shanghai, respectively. Conclusion The 5-year survival rate in China is close to that of most European countries, but still lower than Japan and South Korea, and the gap is gradually narrowing. Region, stage, differentiation, pathological type, and surgical approach can affect 5-year survival in colorectal cancer. Systematic review registration https://www.crd.york.ac.uk/prospero/ identifier, CRD42022357789.
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Affiliation(s)
| | | | | | | | | | | | | | - Haibo Lu
- Department of Outpatient Chemotherapy, Harbin Medical University Cancer Hospital, Harbin, China
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18
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Kazi M, Desouza A, Saklani A. What are the preoperative predictors of a futile pelvic exenteration in rectal cancers? EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2023; 49:633-640. [PMID: 36357296 DOI: 10.1016/j.ejso.2022.10.022] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Revised: 10/06/2022] [Accepted: 10/31/2022] [Indexed: 11/06/2022]
Abstract
INTRODUCTION Early recurrences and deaths after a morbid procedure like pelvic exenteration are devastating events. The present study aimed at determining the incidence and predictors of futile pelvic exenterations. METHODS Consecutive pelvic exenterations for advanced and recurrent rectal adenocarcinomas operated between January 2013 and January 2021 were included with a minimum of six months follow-up. Futility of exenteration was defined as recurrence or death within six months of operation. Multivariate logistic regression was used to define predictors of futility. RESULTS Two-hundred eighty-five patients were included and 61 patients (21.4%) had a futile resection. Poorly differentiated (or signet) histology, presence of lateral pelvic nodes, M1 disease, and the need for pelvic bone resections predicted a futile resection. The probability of futility was 10%, 20%, 35-40%, 55-60%, and >75% when none, one, two, three, and all four of the predictors were present. The model was able to correctly predict futility in 70% of the cases suggesting moderate discrimination, and showed good calibration. CONCLUSIONS Futile pelvic exenterations were observed in one-fifth of patients. Four strong predictors of futility were identified. The risk of early failures was additive when combination of these adverse features was present, and can be used for patient selection and prognostication.
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Affiliation(s)
- Mufaddal Kazi
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, 400012, India; Homi Bhabha National Institute, Mumbai, 400012, India
| | - Ashwin Desouza
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, 400012, India; Homi Bhabha National Institute, Mumbai, 400012, India
| | - Avanish Saklani
- Department of Surgical Oncology, Tata Memorial Hospital, Mumbai, 400012, India; Homi Bhabha National Institute, Mumbai, 400012, India.
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19
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Bong JW, Na Y, Ju Y, Cheong C, Kang S, Lee SI, Min BW. Nomogram for predicting the overall survival of underweight patients with colorectal cancer: a clinical study. BMC Gastroenterol 2023; 23:39. [PMID: 36782150 PMCID: PMC9923908 DOI: 10.1186/s12876-023-02669-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Accepted: 02/07/2023] [Indexed: 02/15/2023] Open
Abstract
BACKGROUND An underweight individual is defined as one whose Body Mass Index (BMI) is < 18.5 kg/m2. Currently, the prognosis in patients with colorectal cancer (CRC) who are also underweight is unclear. METHODS Information on South Korean patients who underwent curative resection for CRC without distant metastasis was collected from health insurance registry data between January 2014 and December 2016. We compared the overall survival (OS) of underweight and non-underweight (BMI ≥ 18.5 kg/m2) patients after adjusting for confounders using propensity score matching. A nomogram to predict OS in the underweight group was constructed using the significant risk factors identified in multivariate analysis. The predictive and discriminative capabilities of the nomogram for predicting 3- and 5-year OS in the underweight group were validated and compared with those of the tumor, node, and metastasis (TNM) staging system in the training and validation sets. RESULTS A total of 23,803 (93.6%) and 1,644 (6.4%) patients were assigned to the non-underweight and underweight groups, respectively. OS was significantly worse in the underweight group than in the non-underweight group for each pathological stage (non-underweight vs. underweight: stage I, 90.1% vs. 77.1%; stage IIA, 85.3% vs. 67.3%; stage IIB/C, 74.9% vs. 52.1%; and stage III, 73.2% vs. 59.4%, P < 0.001). The calibration plots demonstrated that the nomogram exhibited satisfactory consistency with the actual results. The concordance index (C-index) and area under the receiver operating characteristic curve (AUC) of the nomogram exhibited better discriminatory capability than those of the TNM staging system (C-index, nomogram versus TNM staging system: training set, 0.713 versus 0.564, P < 0.001; validation set, 0.691 versus 0.548, P < 0.001; AUC for 3- and 5- year OS, nomogram versus TNM staging system: training set, 0.748 and 0.741 versus 0.610 and 0.601; validation set, 0.715 and 0.753 versus 0.586 and 0.579, respectively). CONCLUSIONS Underweight patients had worse OS than non-underweight patients for all stages of CRC. Our nomogram can guide prognostic predictions and the treatment plan for underweight patients with CRC.
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Affiliation(s)
- Jun Woo Bong
- grid.411134.20000 0004 0474 0479Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148, Gurodong-Ro, Guro-Gu, Seoul, 08308 Republic of Korea
| | - Younghyun Na
- grid.411134.20000 0004 0474 0479Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148, Gurodong-Ro, Guro-Gu, Seoul, 08308 Republic of Korea
| | - Yeonuk Ju
- grid.411134.20000 0004 0474 0479Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148, Gurodong-Ro, Guro-Gu, Seoul, 08308 Republic of Korea
| | - Chinock Cheong
- grid.411134.20000 0004 0474 0479Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148, Gurodong-Ro, Guro-Gu, Seoul, 08308 Republic of Korea
| | - Sanghee Kang
- grid.411134.20000 0004 0474 0479Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148, Gurodong-Ro, Guro-Gu, Seoul, 08308 Republic of Korea
| | - Sun Il Lee
- grid.411134.20000 0004 0474 0479Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148, Gurodong-Ro, Guro-Gu, Seoul, 08308 Republic of Korea
| | - Byung Wook Min
- Department of Surgery, Korea University Guro Hospital, Korea University College of Medicine, 148, Gurodong-Ro, Guro-Gu, Seoul, 08308, Republic of Korea.
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20
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Huang J, Zhang Y, Zhou J, Fang M, Wu X, Luo Y, Huang Q, Ouyang Y, Xiao S. Development and validation of a prognostic nomogram for patients with stage II colon mucinous adenocarcinoma. Int J Colorectal Dis 2022; 37:2173-2184. [PMID: 36149446 DOI: 10.1007/s00384-022-04251-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/14/2022] [Indexed: 02/04/2023]
Abstract
PURPOSE Mucinous histology is generally considered as a risk factor of prognosis in stage II colon cancer, but there is no appropriate model for prognostic evaluation and treatment decision in patients with stage II colon mucinous adenocarcinoma (C-MAC) Thus, it is urgent to develop a comprehensive, individualized evaluation tool to reflect the heterogeneity of stage II C-MAC. METHODS Patients with stage II C-MAC who underwent surgical treatment in the Surveillance, Epidemiology, and End Results Program were enrolled and randomly divided into training cohort (70%) and internal validation cohort (30%). Prognostic predictors which were determined by univariate and multivariate analysis in the training cohort were included in the nomogram. The calibration curves, decision curve analysis, X-tile analysis, and Kaplan-Meier curve of the nomogram were validated in the internal validation cohort. RESULTS Three thousand seven hundred sixty-two patients of stage II C-MAC were enrolled. The age, pathological T (pT) stage, tumor number, serum carcinoembryonic antigen (CEA), and perineural invasion (PNI) were independent predictors of overall survival (OS), which were used to establish a nomogram. Calibration curves of the nomogram indicated good consistency between nomogram prediction and actual survival for 1-, 3- and 5-year OS. Besides, patients with stage II C-MAC could be divided into high-, middle-, and low-risk subgroups by the nomogram. Further subgroup analysis indicated that patients in the high-risk group could have a survival benefit from chemotherapy after surgical treatment. CONCLUSIONS We established the first nomogram to accurately predict the survival of stage II C-MAC patients who underwent surgical treatment. In addition, the nomogram identified low-, middle-, and high-risk subgroups of patients and found chemotherapy might improve survival in the high-risk subgroup of stage II C-MAC patients.
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Affiliation(s)
- Jia Huang
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China
- The First Affiliated Hospital, Department of Ultrasound Medicine, Hengyang Medical School, University of South China Hengyang, Hunan, People's Republic of China
| | - Yiwei Zhang
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China
| | - Jia Zhou
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China
- The First Affiliated Hospital, Department of Ultrasound Medicine, Hengyang Medical School, University of South China Hengyang, Hunan, People's Republic of China
| | - Min Fang
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Xiaofeng Wu
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China
| | - Yuhang Luo
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China
| | - Qiulin Huang
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
| | - Yujuan Ouyang
- Nuclear Industrial Hygiene School, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
| | - Shuai Xiao
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, People's Republic of China.
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, People's Republic of China.
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21
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Zhang Y, Chen Y, Huang J, Wu X, Tang R, Huang Q, Xu Y, Peng X, Fu K, Xiao S. Mucinous histology is associated with poor prognosis in locally advanced colorectal adenocarcinoma treated with postoperative first-line adjuvant chemotherapy: A systematic review and meta-analysis. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2022; 48:2075-2081. [PMID: 35768312 DOI: 10.1016/j.ejso.2022.06.024] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 06/04/2022] [Accepted: 06/19/2022] [Indexed: 12/27/2022]
Abstract
PURPOSE Postoperative adjuvant chemotherapy followed surgery is the standard management for localized advanced colorectal carcinoma (CRC). Mucinous adenocarcinoma (MAC) is a peculiar histological subtype of CRC, but the prognosis of MAC patients is controversial. The objective of this study is to assess the implication of MAC in survival of patients treated with surgery and firs-line adjuvant chemotherapy. METHODS Studies describing outcomes for advanced MAC and non-specific adenocarcinoma (AC) of CRC patients treated with first-line postoperative adjuvant chemotherapy followed surgery were searched in PubMed, Embase, Medline, EBSCO, Wiley, and Cochrane Library (January 1963-August 2021). Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) for MAC to AC were extracted. Random-effects model was used for calculating the pooled HRs and 95% confidence interval (CI). RESULTS This meta-analysis is comprised of 8 studies involving a total of 124,303 CRC patients treated with first-line adjuvant chemotherapy followed surgery. The pooled HR for MAC was 1.23 (95% CI, 1.07-1.41, p < 0.01, I2 = 80%), and the DFS (HR, 2.95, 95% CI, 1.22-7.14) of MAC patients were significantly poorer than AC patients. Similar results were also observed in stage III and FOLFOX regimen subgroups. CONCLUSION MAC was a risk factor for prognosis of localized advanced CRC patients treated with postoperative first-line adjuvant chemotherapy. Thus, the role of first-line adjuvant chemotherapy regimens should be further studied in these MAC patients.
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Affiliation(s)
- Yiwei Zhang
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Yuqiao Chen
- Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China
| | - Jia Huang
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Xiaofeng Wu
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Rong Tang
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Qiulin Huang
- The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Yunhua Xu
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China
| | - Xiuda Peng
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
| | - Kai Fu
- Institute of Molecular Precision Medicine and Hunan Key Laboratory of Molecular Precision Medicine, Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
| | - Shuai Xiao
- The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China; The First Affiliated Hospital, Department of Gastrointestinal Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, China.
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22
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Predictors of Long-Time Survivors in Nonmetastatic Colorectal Signet Ring Cell Carcinoma: A Large Population-Based Study. Gastroenterol Res Pract 2022; 2022:5393571. [PMID: 36032271 PMCID: PMC9402301 DOI: 10.1155/2022/5393571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Accepted: 07/12/2022] [Indexed: 11/18/2022] Open
Abstract
Background Colorectal signet ring cell carcinoma (SRCC) is a rare and distinct subtype of colorectal cancer (CRC), with extremely poor prognosis and aggressive tumor biological behavior. In this study, we aimed to analyze the clinicopathological characteristics and to identify the independent predictors of long-time survivors (LTSs) of nonmetastatic colorectal SRCC. Methods Patients diagnosed with nonmetastatic colorectal SRCC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We compared and analyzed the clinicopathological characteristics between LTSs (patients survived over 5 years) and non-LTSs (patients survived of or less than 5 years). Afterwards, multivariate logistic regression analysis was used to identify independent predictors of LTSs, which were further used to construct a nomogram model to predict the probability of being LTSs. Results We enrolled 2050 patients with nonmetastatic colorectal SRCC, consisting of 1441 non-LTSs and 609 LTSs. Multivariate logistic regression analysis revealed that race, marital status, tumor infiltration, lymph node involvement, and primary tumor treatment were independent predictors of LTSs. In addition, these five parameters were incorporated into a nomogram model to predict the probability of being LTSs. In terms of the model performance, the calibration curve revealed good agreement between observed and predicted probability of LTSs, and receiving operator characteristic curve showed acceptable discriminative capacity in the training and validation cohorts. Conclusion Collectively, we analyzed and profiled the clinicopathological characteristics of LTSs in patients with nonmetastatic colorectal SRCC. Race, marital status, T stage, N stage, and primary tumor treatment were independent predictors of LTSs.
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Ginghina O, Hudita A, Zamfir M, Spanu A, Mardare M, Bondoc I, Buburuzan L, Georgescu SE, Costache M, Negrei C, Nitipir C, Galateanu B. Liquid Biopsy and Artificial Intelligence as Tools to Detect Signatures of Colorectal Malignancies: A Modern Approach in Patient's Stratification. Front Oncol 2022; 12:856575. [PMID: 35356214 PMCID: PMC8959149 DOI: 10.3389/fonc.2022.856575] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 02/16/2022] [Indexed: 01/19/2023] Open
Abstract
Colorectal cancer (CRC) is the second most frequently diagnosed type of cancer and a major worldwide public health concern. Despite the global efforts in the development of modern therapeutic strategies, CRC prognosis is strongly correlated with the stage of the disease at diagnosis. Early detection of CRC has a huge impact in decreasing mortality while pre-lesion detection significantly reduces the incidence of the pathology. Even though the management of CRC patients is based on robust diagnostic methods such as serum tumor markers analysis, colonoscopy, histopathological analysis of tumor tissue, and imaging methods (computer tomography or magnetic resonance), these strategies still have many limitations and do not fully satisfy clinical needs due to their lack of sensitivity and/or specificity. Therefore, improvements of the current practice would substantially impact the management of CRC patients. In this view, liquid biopsy is a promising approach that could help clinicians screen for disease, stratify patients to the best treatment, and monitor treatment response and resistance mechanisms in the tumor in a regular and minimally invasive manner. Liquid biopsies allow the detection and analysis of different tumor-derived circulating markers such as cell-free nucleic acids (cfNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs) in the bloodstream. The major advantage of this approach is its ability to trace and monitor the molecular profile of the patient's tumor and to predict personalized treatment in real-time. On the other hand, the prospective use of artificial intelligence (AI) in medicine holds great promise in oncology, for the diagnosis, treatment, and prognosis prediction of disease. AI has two main branches in the medical field: (i) a virtual branch that includes medical imaging, clinical assisted diagnosis, and treatment, as well as drug research, and (ii) a physical branch that includes surgical robots. This review summarizes findings relevant to liquid biopsy and AI in CRC for better management and stratification of CRC patients.
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Affiliation(s)
- Octav Ginghina
- Department II, University of Medicine and Pharmacy “Carol Davila” Bucharest, Bucharest, Romania
- Department of Surgery, “Sf. Ioan” Clinical Emergency Hospital, Bucharest, Romania
| | - Ariana Hudita
- Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
| | - Marius Zamfir
- Department of Surgery, “Sf. Ioan” Clinical Emergency Hospital, Bucharest, Romania
| | - Andrada Spanu
- Department of Surgery, “Sf. Ioan” Clinical Emergency Hospital, Bucharest, Romania
| | - Mara Mardare
- Department of Surgery, “Sf. Ioan” Clinical Emergency Hospital, Bucharest, Romania
| | - Irina Bondoc
- Department of Surgery, “Sf. Ioan” Clinical Emergency Hospital, Bucharest, Romania
| | | | - Sergiu Emil Georgescu
- Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
| | - Marieta Costache
- Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
| | - Carolina Negrei
- Department of Toxicology, University of Medicine and Pharmacy “Carol Davila” Bucharest, Bucharest, Romania
| | - Cornelia Nitipir
- Department II, University of Medicine and Pharmacy “Carol Davila” Bucharest, Bucharest, Romania
- Department of Oncology, Elias University Emergency Hospital, Bucharest, Romania
| | - Bianca Galateanu
- Department of Biochemistry and Molecular Biology, University of Bucharest, Bucharest, Romania
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Kazi M, Jain D, Padhy AS, Menon M, Desouza A, Sukumar V, Gori J, Ostwal V, Ankathi SK, Saklani A. Optimal neoadjuvant strategy for signet ring cell carcinoma of the rectum-Is TNT the solution? J Surg Oncol 2021; 124:1417-1430. [PMID: 34351625 DOI: 10.1002/jso.26637] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 07/16/2021] [Accepted: 07/25/2021] [Indexed: 12/21/2022]
Abstract
INTRODUCTION The results of total neoadjuvant therapy (TNT) for locally advanced rectal cancers (LARC) cannot be extrapolated to signet-ring cell cancers (SRCC) that have an extremely aggressive biology. METHODS A retrospective study comparing long course chemoradiation (CTRT) against short course radiation (SCRT) and 12 weeks of chemotherapy for high-risk LARC. Primary endpoints were treatment failure and disease-free survival (DFS) RESULTS: CTRT was given to 74 (59.7%) and SCRT/Chemotherapy to 50 patients (40.3%). Additional chemotherapy was required in 54.1% and 28%, respectively. Except for nodal staging, no other MRI parameter down-staged. Treatment failures were seen in 33.9% and 25.8% had progression. The peritoneum was the commonest site of progression (59.4%). Of the patients that were surgically explored, 63.7% had R0 resections and pathological complete response was seen in 9.7%. At a median follow-up of 35 months, 56.5% had DFS events with a 3-year DFS of 39.5%. Recurrences were noted in 45.1% after curative resections and the 3-year OS/DFS of these patients were 67.2%/56.4%. On multivariate regression, the type of preoperative therapy did not influence treatment failures or DFS. CONCLUSIONS SRCC is a very aggressive disease and none of the treatment strategies could show superiority over the other with very high peritoneal progression rates and relapses.
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Affiliation(s)
- Mufaddal Kazi
- Department of Surgical Oncology, Division of Colorectal Surgery, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Divakar Jain
- Department of Surgical Oncology, Division of Colorectal Surgery, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Amita Sekhar Padhy
- Department of Surgical Oncology, Division of Colorectal Surgery, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Munita Menon
- Department of Pathology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Ashwin Desouza
- Department of Surgical Oncology, Division of Colorectal Surgery, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vivek Sukumar
- Department of Surgical Oncology, Division of Colorectal Surgery, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Jayesh Gori
- Department of Surgical Oncology, Division of Colorectal Surgery, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Vikas Ostwal
- Department of Medical Oncology, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Suman Kumar Ankathi
- Department of Radio-diagnosis, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Avanish Saklani
- Department of Surgical Oncology, Division of Colorectal Surgery, Tata Memorial Hospital and Homi Bhabha National Institute, Mumbai, Maharashtra, India
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25
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Suthar M, Baheti AD, Ankathi SK, Choudhari A, Haria PD, Engineer R, Ostwal V, Ramadwar MS, Desouza A, Saklani A. MRI features of signet ring rectal cancer. Abdom Radiol (NY) 2021; 46:5536-5549. [PMID: 34427742 DOI: 10.1007/s00261-021-03250-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 08/10/2021] [Accepted: 08/11/2021] [Indexed: 12/28/2022]
Abstract
PURPOSE Signet Ring Rectal Cancer (SRRC) of rectum is rare high-grade subtype with poor prognosis and characteristic histopathology. We evaluated its imaging appearance and correlated its outcomes. MATERIALS AND METHODS We conducted a retrospective review of the rectal MRIs of 97 patients with rectal SRRC, evaluating tumor morphology, T2 signal, length, location, pattern of tumor growth, nodal status and location, EMVI (extramural vascular invasion), site of metastases, and response to chemotherapy. The tumor signal on T2W images was categorized into intermediate, T2 hyperintense, and fluid/mucin bright. Imaging findings were correlated with risk of metastatic/ recurrent disease, disease-free survival, and overall survival. RESULTS The median age of patients of SRRC in our study was 35 years and more frequently found in male patients. The common imaging features of SRRC were T2-hyperintense signal (63%), infiltrative growth pattern (76%), positive MR CRM (Circumferential Resection Margin on MRI) (84%), presence of EMVI (51%), and advanced T and N stage (97% and 84%, respectively). Peritoneum and nodes were the most common sites of metastases. Raised serum CEA (Carcino-embryonic Antigen) levels, positive MR CRM status, extramesorectal adenopathy, and advanced N stage had statistically significant predictive value for recurrence or metastases. Elevated serum CEA levels (p = 0.019) and intermediate T2 signal (p = 0.012) demonstrated significant independent association with poor overall survival, while advanced N stage (p = 0.033) demonstrated significant independent association with worse disease-free survival in multivariate analysis. CONCLUSION SRRC affected young patients and demonstrated T2-hyperintense signal and subepithelial spread in an infiltrative pattern. Elevated CEA levels and T2-intermediate signal intensity are independent predictors for worse overall survival and advanced nodal stage is independent prognostic factor of poor disease-free survival. MRI rectum can pinpoint the pathology given the distinct MRI morphology and age of presentation.
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Affiliation(s)
- Meena Suthar
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
| | - Akshay D Baheti
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India.
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India.
| | - Suman K Ankathi
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
| | - Amit Choudhari
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
| | - Purvi D Haria
- Department of Radio-Diagnosis, Tata Memorial Centre, Mumbai, India
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
| | - Reena Engineer
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of Radiation Oncology, Tata Memorial Centre, Mumbai, India
| | - Vikas Ostwal
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of Medical Oncology, Tata Memorial Centre, Mumbai, India
| | - Mukta S Ramadwar
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of Pathology, Tata Memorial Centre, Mumbai, India
| | - Ashwin Desouza
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of GI Surgical Oncology, Tata Memorial Centre, Mumbai, India
| | - Avanish Saklani
- Tata Memorial Hospital, Homi Bhabha National Institute, Dr. Ernest Borges Road, Mumbai, Maharashtra, 400012, India
- Department of GI Surgical Oncology, Tata Memorial Centre, Mumbai, India
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Van Herck Y, Feyaerts A, Alibhai S, Papamichael D, Decoster L, Lambrechts Y, Pinchuk M, Bechter O, Herrera-Caceres J, Bibeau F, Desmedt C, Hatse S, Wildiers H. Is cancer biology different in older patients? THE LANCET HEALTHY LONGEVITY 2021; 2:e663-e677. [DOI: 10.1016/s2666-7568(21)00179-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Revised: 07/14/2021] [Accepted: 07/15/2021] [Indexed: 12/13/2022]
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Choi BW, Kang S, Bae SU, Jeong WK, Baek SK, Song BI, Won KS, Kim HW. Prognostic value of metabolic parameters on 18F-fluorodeoxyglucose positron tomography/computed tomography in classical rectal adenocarcinoma. Sci Rep 2021; 11:12947. [PMID: 34155222 PMCID: PMC8217562 DOI: 10.1038/s41598-021-92118-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 06/03/2021] [Indexed: 02/07/2023] Open
Abstract
We aimed to investigate the prognostic value of the metabolic parameters of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in classical rectal adenocarcinoma (CRAC). We retrospectively reviewed 149 patients with CRAC who underwent preoperative 18F-FDG PET/CT at initial diagnosis followed by curative surgical resection. 18F-FDG PET/CT metabolic parameters including maximum standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) for disease-free survival (DFS) and overall survival (OS) were evaluated for prognostic significance by univariate and multivariate analyses, along with conventional risk factors including pathologic T (pT) stage, lymph node (LN) metastasis, lymphovascular invasion (LVI), perineural invasion (PNI), and preoperative carcinoembryonic antigen (CEA) level. On univariate analysis, high pT stage, positive LN metastasis, LVI, PNI, MTV, and TLG were significant prognostic factors affecting DFS (all P < 0.05), while CEA level, high pT stage, positive LN metastasis, LVI, PNI, MTV, and TLG affected OS (all P < 0.05). On multivariate analysis, positive LN metastasis, LVI, MTV, and TLG were independent prognostic factors affecting DFS (all P < 0.05), while CEA level, positive LN metastasis, and MTV affected OS (all P < 0.05). Thus, the volume-based metabolic parameters from preoperative 18F-FDG PET/CT scans are independent prognostic factors in patients with CRAC.
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Affiliation(s)
- Byung Wook Choi
- Department of Nuclear Medicine, Daegu Catholic University Medical Center, Daegu Catholic University School of Medicine, Daegu, Republic of Korea
| | - Sungmin Kang
- Department of Nuclear Medicine, Daegu Catholic University Medical Center, Daegu Catholic University School of Medicine, Daegu, Republic of Korea
| | - Sung Uk Bae
- Division of Colorectal Surgery, Department of Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Woon Kyung Jeong
- Division of Colorectal Surgery, Department of Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Seong Kyu Baek
- Division of Colorectal Surgery, Department of Surgery, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Bong-Il Song
- Department of Nuclear Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, 1035, Dalgubeol-daero, Dalseo-gu, Daegu, Republic of Korea
| | - Kyoung Sook Won
- Department of Nuclear Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, 1035, Dalgubeol-daero, Dalseo-gu, Daegu, Republic of Korea
| | - Hae Won Kim
- Department of Nuclear Medicine, Keimyung University Dongsan Hospital, Keimyung University School of Medicine, 1035, Dalgubeol-daero, Dalseo-gu, Daegu, Republic of Korea.
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28
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The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surveillance and Survivorship Care of Patients After Curative Treatment of Colon and Rectal Cancer. Dis Colon Rectum 2021; 64:517-533. [PMID: 33591043 DOI: 10.1097/dcr.0000000000001984] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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29
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Kou FR, Zhang YZ, Xu WR. Prognostic nomograms for predicting overall survival and cause-specific survival of signet ring cell carcinoma in colorectal cancer patients. World J Clin Cases 2021; 9:2503-2518. [PMID: 33889615 PMCID: PMC8040180 DOI: 10.12998/wjcc.v9.i11.2503] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 01/28/2021] [Accepted: 02/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Signet ring cell carcinoma (SRCC) is an uncommon subtype in colorectal cancer (CRC), with a short survival time. Therefore, it is imperative to establish a useful prognostic model. As a simple visual predictive tool, nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years. Until now, there has been no nomogram to predict the outcome of CRC patients with SRCC.
AIM To build effective nomograms for predicting overall survival (OS) and cause-specific survival (CSS) of CRC patients with SRCC.
METHODS Data were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms. Performance of the nomograms was assessed by concordance index, calibration curves, and receiver operating characteristic (ROC) curves. ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis (TNM) staging system. Patients were classified as high-risk, moderate-risk, and low-risk groups using the novel nomograms. Kaplan-Meier curves were plotted to compare survival differences.
RESULTS In total, 1230 patients were included. The concordance index of the nomograms for OS and CSS were 0.737 (95% confidence interval: 0.728-0.747) and 0.758 (95% confidence interval: 0.738-0.778), respectively. The calibration curves and ROC curves demonstrated good predictive accuracy. The 1-, 3-, and 5-year area under the curve values of the nomogram for predicting OS were 0.796, 0.825 and 0.819, in comparison to 0.743, 0.798, and 0.803 for the TNM staging system. In addition, the 1-, 3-, and 5-year area under the curve values of the nomogram for predicting CSS were 0.805, 0.847 and 0.863, in comparison to 0.740, 0.794, and 0.800 for the TNM staging system. Based on the novel nomograms, stratified analysis showed that the 5-year probability of survival in the high-risk, moderate-risk, and low-risk groups was 6.8%, 37.7%, and 67.0% for OS (P < 0.001), as well as 9.6%, 38.5%, and 67.6% for CSS (P < 0.001), respectively.
CONCLUSION Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC, which are superior to the conventional TNM staging system.
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Affiliation(s)
- Fu-Rong Kou
- Department of Day Oncology Unit, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Yang-Zi Zhang
- Department of Radiation Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Wei-Ran Xu
- Department of Oncology, Peking University International Hospital, Beijing 102206, China
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Wu M, Huang M, He C, Chen C, Li H, Wang J, Liu M, Fu G, Lei Z, Chu X. Risk of Second Primary Malignancies Based on the Histological Subtypes of Colorectal Cancer. Front Oncol 2021; 11:650937. [PMID: 33777813 PMCID: PMC7988191 DOI: 10.3389/fonc.2021.650937] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Accepted: 02/15/2021] [Indexed: 01/02/2023] Open
Abstract
Background: Previous studies have revealed an increased risk of second primary malignancies (SPMs) after colorectal cancer (CRC); however, no previous investigation has quantified differences in the risk of SPMs based on the histological subtypes of first primary CRC. Methods: Patients diagnosed with first primary CRC between 2000 and 2011 were identified from the Surveillance, Epidemiology, and End Results cancer registries. The patients were divided into three cohorts: classical adenocarcinoma (CA), mucinous adenocarcinoma (MA), and signet-ring cell carcinoma (SRCC). Standardized incidence ratios were calculated to assess the risk of SPMs among the patients. Results: Overall risk of SPMs was significantly higher among patients with three histological subtypes of CRC than in the general population. The risk of esophagus cancer was significantly increased in SRCC. The risk of small intestine, colon and rectum, and corpus uteri cancers was high in three histological subtypes, with the highest risk observed in SRCC, followed by MA. Increased risks of second stomach, uterus, urinary bladder, kidney, and thyroid cancers were only observed in CA patients, while increased risk of second renal pelvis cancer was limited to MA patients. Furthermore, the high overall risk of SPMs in CA patients persisted regardless of clinicopathological factors. After surgery combined with chemotherapy treatment, CA patients were more prone to developing second small intestine, colon and rectum cancers than those treated with surgery only. A lower second prostate cancer risk was observed in rectal CA patients treated with surgery combined with radiotherapy than in patients treated with surgery only. Conclusion: The present study revealed that the risk of developing SPMs after CRC varied based on the histological subtypes of the first primary CRC. Although the mechanisms underlying the observed patterns of SPM risk remain unknown, the study provided insights into future cancer surveillance based on the histological subtypes of CRC.
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Affiliation(s)
- Meijuan Wu
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Mengxi Huang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Chenglong He
- Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Cheng Chen
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Huiyu Li
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Jing Wang
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Mengyan Liu
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China
| | - Gongbo Fu
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Zengjie Lei
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
| | - Xiaoyuan Chu
- Department of Medical Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, China.,Department of Medical Oncology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China
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Kazi M, Nekkanti SS, Rohila J, Patel S, Sukumar V, Desouza A, Saklani A. Impact of surgical staging for aggressive histology rectal cancers: a retrospective review. ANZ J Surg 2021; 91:E119-E122. [PMID: 33377582 DOI: 10.1111/ans.16496] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 11/25/2020] [Accepted: 11/28/2020] [Indexed: 12/24/2022]
Abstract
BACKGROUND Poorly differentiated adenocarcinomas and signet ring adenocarcinomas are aggressive histological subtypes of rectal cancer with a high incidence of occult peritoneal metastasis. METHODS This was a retrospective review of aggressive histology of rectal cancer patients who underwent pre-treatment surgical staging as part of ovarian transposition or ostomy creation for diversion at a single tertiary cancer centre between January 2014 and December 2019. RESULTS A total of 117 patients underwent surgical staging and were deemed non-metastatic on imaging. Surgical staging led to the detection of metastasis in 29.9% of patients. This led to modification in treatment protocol in 20.5% and change in intent of therapy in 15.4%. The majority (80%) was found to have peritoneal disease with peritoneal carcinomatosis index <17. Only T4 disease predicted the presence of metastasis on surgical staging with an odds ratio of 2.69 (P = 0.035). CONCLUSIONS A significant proportion of patients with aggressive histology rectal cancers are upstaged after surgical staging. Further investigation of this tool for staging is warranted.
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Affiliation(s)
- Mufaddal Kazi
- Department of Colorectal Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Sri Siddhartha Nekkanti
- Department of Colorectal Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Jitender Rohila
- Department of Colorectal Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Swapnil Patel
- Department of Colorectal Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Vivek Sukumar
- Department of Colorectal Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Ashwin Desouza
- Department of Colorectal Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
| | - Avanish Saklani
- Department of Colorectal Surgical Oncology, Tata Memorial Hospital, Homi Bhabha National Institute, Mumbai, India
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32
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Fadel MG, Malietzis G, Constantinides V, Pellino G, Tekkis P, Kontovounisios C. Clinicopathological factors and survival outcomes of signet-ring cell and mucinous carcinoma versus adenocarcinoma of the colon and rectum: a systematic review and meta-analysis. Discov Oncol 2021; 12:5. [PMID: 35201441 PMCID: PMC8762524 DOI: 10.1007/s12672-021-00398-6] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Accepted: 01/27/2021] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Histological subtypes of colorectal cancer may be associated with varied prognostic features. This systematic review and meta-analysis aimed to compare clinicopathological characteristics, recurrence and overall survival between colorectal signet-ring cell (SC) and mucinous carcinoma (MC) to conventional adenocarcinoma (AC). METHODS A literature search of MEDLINE, EMBASE, Ovid and Cochrane Library was performed for studies that reported data on clinicopathological and survival outcomes on SC and/or MC versus AC from January 1985 to May 2020. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed. RESULTS Thirty studies of 1,087,055 patients were included: 11,510 (1.06%) with SC, 110,179 (10.13%) with MC and 965,366 (88.81%) with AC. Patients with SC were younger than patients with AC (WMD - 0.47; 95% CI - 0.84 to -0.10; I2 88.6%; p = 0.014) and more likely to have right-sided disease (OR 2.12; 95% CI 1.72-2.60; I2 82.9%; p < 0.001). Locoregional recurrence at 5 years was more frequent in patients with SC (OR 2.81; 95% CI 1.40-5.65; I2 0.0%; p = 0.004) and MC (OR 1.92; 95% CI 1.18-3.15; I2 74.0%; p = 0.009). 5-year overall survival was significantly reduced when comparing SC and MC to AC (HR 2.54; 95% CI 1.98-3.27; I2 99.1%; p < 0.001 and HR 1.38; 95% CI 1.19-1.61; I2 98.6%; p < 0.001, respectively). CONCLUSION SC and MC are associated with right-sided lesions, advanced stage at presentation, higher rates of recurrence and poorer overall survival. This has strong implications towards surgical and oncological management and surveillance of colorectal cancer.
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Affiliation(s)
- Michael G Fadel
- Department of Colorectal Surgery, Chelsea and Westminster Hospital, London, UK.
| | - George Malietzis
- Department of Surgery and Cancer, Imperial College, London, UK
- Department of Colorectal Surgery, Royal Marsden Hospital, London, UK
| | | | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Università degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
| | - Paris Tekkis
- Department of Colorectal Surgery, Chelsea and Westminster Hospital, London, UK
- Department of Surgery and Cancer, Imperial College, London, UK
- Department of Colorectal Surgery, Royal Marsden Hospital, London, UK
| | - Christos Kontovounisios
- Department of Colorectal Surgery, Chelsea and Westminster Hospital, London, UK
- Department of Surgery and Cancer, Imperial College, London, UK
- Department of Colorectal Surgery, Royal Marsden Hospital, London, UK
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33
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Ozawa H, Yamauchi S, Nakanishi H, Sakamoto J, Fujita S, Sugihara K. Clinical impact of non-predominant histopathological subtypes on the long-term prognosis of colorectal cancer patients in Japan. Int J Colorectal Dis 2020; 35:2257-2266. [PMID: 32772123 DOI: 10.1007/s00384-020-03707-7] [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] [Accepted: 07/23/2020] [Indexed: 02/04/2023]
Abstract
PURPOSE We performed a retrospective study to clarify the long-term prognosis of patients with histopathological high-grade colorectal cancer (CRC). METHODS We reviewed data from 24 institutions for 18,360 patients with pStage I to III CRC who had undergone curative surgery between 2004 and 2012. The patients were classified into seven groups according to the proportion of the histopathological component: classical adenocarcinoma (CAC) group, M-l and M-h groups (< 50% and ≥ 50% mucinous adenocarcinoma, respectively), P-l and P-h groups (< 50% and ≥ 50% poorly differentiated adenocarcinoma, respectively), and S-l and S-h groups (< 50% and ≥ 50% signet-ring cell carcinoma (SRCC), respectively). RESULTS The 5-year recurrence-free survival (RFS) rates of the M-l, P-l, and S-l groups were 75.5%, 68.4%, and 52.4%, respectively, and were significantly lower than those of the CAC group (83.5%, hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.01-1.48, p = 0.0365; HR 1.60, 95% CI 1.32-1.91, p < 0.0001; HR 2.61, 95% CI 1.30-4.57, p = 0.0090, respectively). The 5-year RFS of the P-l and S-l groups was as poor as that of the P-h and S-h groups, respectively (HR 0.87, 95% CI 0.68-1.10, p = 0.25; HR 0.90, 95% CI 0.37-2.13, p = 0.81, respectively). The histopathological component of the S-l group was an independent factor affecting overall survival in multivariate analysis. CONCLUSION The long-term prognoses of the non-predominant poorly differentiated adenocarcinoma (PAC) groups were as poor as those of the predominant group. In particular, the histopathological component of the P-l and S-l groups could be classified into predominant PAC and SRCC subtypes for appropriate prognostic predictions.
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Affiliation(s)
- Heita Ozawa
- Department of Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan.
| | - Shinichi Yamauchi
- Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
| | - Hiroki Nakanishi
- Department of Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan
| | - Junichi Sakamoto
- Department of Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan
| | - Shin Fujita
- Department of Surgery, Tochigi Cancer Center, 4-9-13 Yohnan, Utsunomiya, Tochigi, 320-0834, Japan
| | - Kenichi Sugihara
- Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan
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Barresi V, Pedrazzani C. Colorectal signet ring cell carcinoma: advancing research in a rare cancer. Future Oncol 2020; 16:1161-1163. [PMID: 32351144 DOI: 10.2217/fon-2020-0242] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Affiliation(s)
- Valeria Barresi
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | - Corrado Pedrazzani
- Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, Unit of General and Hepatobiliary Surgery, University of Verona, Verona, Italy
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