Background: KRAS mutations, microsatellite instability, and tumor location have been found to be significant prognostic factors in colorectal cancer. The interaction between these variables and its effect on overall survival in nonmetastatic colon cancer has not been well elucidated.
Methods: The National Cancer Database (2010-2016) was queried for patients with stage I-III colon cancer and known microsatellite instability and KRAS status undergoing curative resection.
Results: A total of 5,292 patients were identified: 60.4% had right-sided cancers, 36.4% had KRAS mutations, and 15.6% had microsatellite instability. Right-sided tumors were more likely to have microsatellite instability and KRAS mutations compared to left-sided tumors. On univariable analysis, KRAS mutations and microsatellite instability status were not associated with differences in survival, whereas right-sided cancers had worse overall survival compared to left-sided cancers (hazard ratio 1.32, 95% confidence interval: 1.18-1.47). On multivariable analysis, right-sided location, KRAS mutations, and microsatellite instability were not independent prognostic factors. However, a significant interaction between laterality and KRAS status was observed. In patients with mutated KRAS cancers, left-sided tumors were at increased risk of death compared to right-sided tumors (hazard ratio: 1.30, 95% confidence interval: 1.03-1.63), whereas in patients with wild-type KRAS cancers, left-sided tumors were at decreased risk of death (hazard ratio: 0.81, 95% confidence interval: 0.67-0.97).
Conclusion: In patients with stage I-III colon cancer, laterality, KRAS mutation, and microsatellite instability status were not independently prognostic after curative resection. However, the effect of laterality was opposite based on KRAS status, with left-sided (compared to right-sided) tumors associated with worse overall survival in mutated KRAS patients and better overall survival in wild-type KRAS individuals. Laterality itself may not be an independent prognostic factor but a reflection of differing genetic profiles within the colon.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.surg.2021.10.043 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mutation Analysis of TMB-High Colorectal Cancer: Insights Into Molecular Pathways and Clinical Implications.
Cancer Sci
January 2025
Oncology Innovation Center, Fujita Health University, Toyoake, Aichi, Japan.
Colorectal cancer (CRC) is well characterized in terms of genetic mutations and the mechanisms by which they contribute to carcinogenesis. Mutations in APC, TP53, and KRAS are common in CRC, indicating key roles for these genes in tumor development and progression. However, for certain tumors with low frequencies of these mutations that are defined by tumor location and molecular phenotypes, a carcinogenic mechanism dependent on BRAF mutations has been proposed.
View Article and Find Full Text PDFGender and sex differences in colorectal cancer screening, diagnosis and treatment.
Clin Transl Oncol
January 2025
Department of Medical Oncology, University Hospital of Navarra, Instituto de Investigación Sanitaria de Navarra, IdISNA, Navarra, Spain.
Males have a higher incidence and mortality rate from colorectal cancer (CRC) compared with females. This review examines the reasons for these differences, including risk factors, screening participation, interpretation of screening tests, presentation and tumour types, pathophysiology (particularly the impact of sex hormones on tumour-related gene expression, microsatellite instability, micro-RNA expression, and the tumour microenvironment), and the efficacy and toxicity of treatment. Sex differences in hormones and body composition are responsible for some of the sexual dimorphism in CRC incidence and outcomes, particularly the pathophysiology, CRC presentation, the pharmacokinetics of cytotoxic therapies, and the impact of treatment on outcomes.
View Article and Find Full Text PDFPredictive value of NUF2 for prognosis and immunotherapy responses in pan-cancer.
Nan Fang Yi Ke Da Xue Xue Bao
January 2025
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangxi Medical University //Key Laboratory of Biological Molecular Medicine Research, Education Department of Guangxi Zhuang Autonomous Region, Nanning 530021, China.
Objectives: To investigate the association of NUF2 expression with tumor prognosis and its regulatory role in tumor microenvironment.
Methods: We analyzed NUF2 expression, its prognostic value, and is immune-related functions across different cancer types using datasets from the Human Protein Atlas (HPA), TCGA, GTEx, CCLE, and TIMER. RT-qPCR, Western blotting, and immunohistochemistry were used to detect NUF2 expression in liver cancer cell lines and tissue and blood samples from patients with liver cancer.
Genomic profiles and their associations with microsatellite instability status, tumor mutational burden, and programmed death ligand 1 expression in Chinese patients with colorectal cancer.
J Gastrointest Oncol
December 2024
Department of Traditional Chinese Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Background: Colorectal cancer (CRC) is among the most prevalent malignancies globally, with a rising incidence observed in younger demographics. Despite surgical resection remaining the cornerstone of treatment, metastatic CRC poses significant therapeutic challenges. Immunotherapy, a mode of treatment that leverages the patient's immune system, presents a promising frontier in CRC management, particularly for late-stage cases with limited treatment options.
View Article and Find Full Text PDFMolecular subtype of ovarian clear cell carcinoma: an analysis of 80 Chinese patients using the TCGA molecular classification of endometrial cancer.
BMC Cancer
January 2025
Department of Gynecologic Oncology, Fudan University Shanghai Cancer Centre, Shanghai, China.
Background: To assess the utility of the TCGA molecular classification of endometrial cancer in a well-annotated, moderately sized, consecutive cohort of Chinese patients with ovarian clear cell carcinoma (OCCC).
Methods: We performed DNA sequencing on 80 OCCC patients via a panel that contains 520 cancer-related genes. The TCGA molecular subtyping method was utilized for classification.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!