An Original Ferroptosis-Related Gene Signature Effectively Predicts the Prognosis and Clinical Status for Colorectal Cancer Patients

Frontiers in Oncology

Sen Zhang²  Ling Huang²  Yanfei Shao²  Hongtao Jia²  Guang Yang³  Chenxing Wang³  Shuchun Li³  Xiao Yang³  Jing Sun³  Batuer Aikemu³  Hiju Hong³  Minhua Zheng³ 

[1] Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;

关键词: colorectal cancer;    ferroptosis;    gene signature;    prognostic model;    drug sensitivity;   

DOI  :  10.3389/fonc.2021.711776

来源: DOAJ

【 摘 要 】

BackgroundColorectal cancer (CRC) is one of the most common malignant tumors in the world. Ferroptosis is a newly defined form of cell death, distinguished by different morphology, biochemistry, and genetics, and involved in CRC progression and treatment. This study aims to establish a predictive model to elucidate the relationship between ferroptosis and prognosis of CRC patients, to explore the potential value of ferroptosis in therapeutic options.MethodsThe ferroptosis-related genes were obtained from the GeneCards and FerrDb websites. The limma R package was used to screen the differential ferroptosis-related genes (DEGs) in CRC from The Cancer Genome Atlas (TCGA) dataset. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were to establish the 10-gene prognostic signature. The survival and receiver operating characteristic (ROC) curves were illustrated to evaluate the predictive effect of the signature. Besides, independent prognostic factors, downstream functional enrichment, drug sensitivity, somatic mutation status, and immune feature were analyzed. Moreover, all these conclusions were verified by using multiple datasets in International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO).ResultsTen ferroptosis-related gene signature (TFAP2C, SLC39A8, NOS2, HAMP, GDF15, FDFT1, CDKN2A, ALOX12, AKR1C1, ATP6V1G2) was established to predict the prognosis of CRC patients by Lasso cox analysis, demonstrating a good performance on Receiver operating characteristic (ROC) and Kaplan–Meier (K–M) analyses. The CRC patients in the high- or low-risk group showed significantly different fractions of immune cells, such as macrophage cells and CD8+ T cells. Drug sensitivity and somatic mutation status like TP53 were also closely associated with the risk scores.ConclusionsIn this study, we identified a novel ferroptosis-related 10-gene signature, which could effectively predict the prognosis and survival time of CRC patients, and provide meaningful clinical implications for targeted therapy or immunotherapy. Targeting ferroptosis is a good therapeutic option for CRC patients. Further studies are needed to reveal the underlying mechanisms of ferroptosis in CRC.

【 授权许可】

Unknown