结直肠癌
免疫疗法
免疫检查点
免疫系统
亚型
癌症
肿瘤科
微卫星不稳定性
基因
生物
癌症研究
医学
生物信息学
内科学
计算生物学
免疫学
遗传学
计算机科学
程序设计语言
等位基因
微卫星
作者
Zhujiang Dai,Xiang Peng,Yao Guo,Xia Shen,Wenjun Ding,Jihong Fu,Zhonglin Liang,Jinglue Song
标识
DOI:10.1007/s00432-022-04070-6
摘要
Colon cancer presents challenges to clinical diagnosis and management due to its high heterogeneity. For more efficient and convenient diagnosis and treatment of colon cancer, we are committed to characterizing the molecular features of colon cancer by pioneering a classification system based on metabolic pathways.Based on the 113 metabolic pathways and genes collected in the previous stage, we scored and filtered the metabolic pathways of each sample in the training set by ssGSEA, and obtained 16 metabolic pathways related to colon cancer recurrence. In consistent clustering of training set samples with recurrence-related metabolic pathway scores, we identified two robust molecular subtypes of colon cancer (MC1 and MC2). Furthermore, we performed multi-angle analysis on the survival differences of subtypes, metabolic characteristics, clinical characteristics, functional enrichment, immune infiltration, differences with other subtypes, stemness indices, TIDE prediction, and drug sensitivity, and finally constructed colon cancer prognostic model.The results showed that the MC1 subtype had a poor prognosis based on higher immune activity and immune checkpoint gene expression. The MC2 subtype is associated with high metabolic activity and low expression of immune checkpoint genes and a better prognosis. The MC2 subtype was more responsive to PD-L1 immunotherapy than the MC1 subclass. However, we did not observe significant differences in tumor mutational burden between the two.Two molecular subtypes of colon cancer based on metabolic pathways have distinct immune signatures. Constructing prognostic models based on subtype differential genes provides valuable reference for personalized therapy targeting unique tumor metabolic signatures.
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