학술논문
Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases
Original Article-Alimentary Tract
Original Article-Alimentary Tract
Document Type
Academic Journal
Author
Source
Journal of Gastroenterology. March 2023, Vol. 58 Issue 3, p229, 17 p.
Subject
Language
English
ISSN
0944-1174
Abstract
Author(s): Tomotaka Ugai [sup.1] [sup.2], Naohiko Akimoto [sup.1], Koichiro Haruki [sup.1], Tabitha A. Harrison [sup.3], Yin Cao [sup.4] [sup.5] [sup.6], Conghui Qu [sup.3], Andrew T. Chan [sup.7] [sup.8] [sup.9] [sup.10], [...]
Background The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. Methods Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. Results There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (P.sub.trend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (P.sub.interaction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [P.sub.trend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (P.sub.trend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (P.sub.interaction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. Conclusions Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.
Background The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. Methods Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. Results There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (P.sub.trend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (P.sub.interaction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [P.sub.trend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (P.sub.trend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (P.sub.interaction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. Conclusions Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.