Unveiling mitophagy-mediated molecular heterogeneity and development of a risk signature model for colorectal cancer by integrated scRNA-seq and bulk RNA-seq analysis
Han Gao1
Qi Zou1
Linyun Ma2
Keyu Cai1
Yi Sun3
Li Lu1
Donglin Ren1
Bang Hu1
1.Department of General Surgery(Coloproctology),The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China;Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China;Biomedical Innovation Center,The Sixth Affiliated Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China2.Department of Anesthesiology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong,P.R.China3.Department of Pathology,Kingmed Pathology Center,Guangzhou,Guangdong,P.R.China
摘要：Background:Accumulating researchers have recognized mitophagy as a key player in tumors,but few studies have investigated its role in the tumor microenvironment(TME).Advances in the technology of single-cell RNA sequencing(scRNA-seq)have allowed unveiling the concealed features of the TME at cellular resolution.This study aimed to elucidate the role of mitophagy within the TME of colorectal cancer(CRC)and to establish a mitophagy-mediated risk model.
Methods:We assessed mitophagy-related pathway activities at both single-cell and tissue levels.Subsequently,an unsupervised clustering algorithm was employed to identify mitophagy-mediated subtypes.Furthermore,we developed a mitophagy-mediated risk signature(MMRS)using least absolute shrinkage and selection operator(LASSO)Cox analysis and constructed a MMRS model incorporating the risk score and clinical variables.Subsequently,we used quantitative reverse transcription polymerase chain reac-tion analysis to verify the expression of the screened genes.
Results:We retrieved and annotated a total of 14,719 cells from eight samples in the scRNA-seq GSE132465 data set.The activities of mitophagy-related pathways were uniformly upregulated in cancer cells.Integrating with bulk RNA-seq data,we identified two mitophagy-mediated clusters(C1 and C2)with distinct characteristics and prognoses.C2 was identified as a mitophagy-high cluster.Then,we developed a five-gene MMRS via LASSO Cox analysis in The Cancer Genome Atlas(TCGA)cohort.We utilized the GSE39582 cohort to validate the efficacy of our model.The expression of CX3CL1 and INHBB was upregulated in CRC tissues.
Conclusions:The present study identified two mitophagy-mediated CRC subtypes with distinct features.Our MMRS may provide potential therapeutic strategies for CRC.The findings of our work offer novel insights into the involvement of mitophagy in CRC.
机标关键词：signaturedevelopmentintegratedmolecularanalysiscancerbulkrisk
论文发表日期：2024-06-30
在线出版日期：2026-07-17（本平台首次上网日期，不代表文献的发表时间）
页数：12( 239-250 )
英文信息