Identification of stem cell-related subtypes and risk scoring for gastric cancer based on stem genomic profiling

Stem Cell Research & Therapy

Tao Fu¹  Jing Wu²  Renshen Xiang²  Jun Ren²  Wei Song²  Jincheng Fu² 

[1] Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, China;Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, China;Central Laboratory, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, China;

关键词: Gastric cancer;    Stem cell gene sets;    Immune infiltration;    Tumor mutation burden;    Therapeutic response;    Risk score;   

DOI  :  10.1186/s13287-021-02633-x

来源: Springer

【 摘 要 】

BackgroundAlthough numerous studies demonstrate the role of cancer stem cells in occurrence, recurrence, and distant metastases in gastric cancer (GC), little is known about the evolving genetic and epigenetic changes in the stem and progenitor cells. The purpose of this study was to identify the stem cell subtypes in GC and examine their clinical relevance.MethodsTwo publicly available datasets were used to identify GC stem cell subtypes, and consensus clustering was performed by unsupervised machine learning methods. The cancer stem cell (CSC) typing-related risk scoring (RS) model was established through multivariate Cox regression analysis.ResultsCross-platform dataset-based two stable GC stem cell subtypes, namely low stem cell enrichment (SCE_L) and high stem cell enrichment (SCE_H), were prudently identified. Gene set enrichment analysis revealed that the classical oncogenic pathways, immune-related pathways, and regulation of stem cell division were active in SCE_H; ferroptosis, NK cell activation, and post-mutation repair pathways were active in SCE_L. GC stem cell subtypes could accurately predict clinical outcomes in patients, tumor microenvironment cell-infiltration characteristics, somatic mutation landscape, and potential responses to immunotherapy, targeted therapy, and chemotherapy. Additionally, a CSC typing-related RS model was established; it was strongly independent and could accurately predict the patient’s overall survival.ConclusionsThis study demonstrated the complex oncogenic mechanisms underlying GC. The findings provide a basis and reference for the diagnosis and treatment of GC.

【 授权许可】

CC BY