Bulk and single-cell transcriptome profiling reveal necroptosis-based molecular classification, tumor microenvironment infiltration characterization, and prognosis prediction in colorectal cancer

作者：Wenqin Luo, Wenqiang Xiang, Lu Gan, Ji Che, Jing Li, Yichao Wang, Lingyu Han, Ruiqi Gu, Li Ye, Renjie Wang, Xiuping Zhang, Ye Xu, Weixing Dai, Shaobo Mo, Qingguo Li, Guoxiang Cai · 发表于：Journal of Translational Medicine · 年份：2022 · DOI：10.1186/s12967-022-03431-6 · 被引用次数：15 · 研究领域：Ferroptosis and cancer prognosis、Cell death mechanisms and regulation、Phagocytosis and Immune Regulation

BACKGROUND: Necroptosis is a new form of programmed cell death that is associated with cancer initiation, progression, immunity, and chemoresistance. However, the roles of necroptosis-related genes (NRGs) in colorectal cancer (CRC) have not been explored comprehensively. METHODS: In this study, we obtained NRGs and performed consensus molecular subtyping by "ConsensusClusterPlus" to determine necroptosis-related subtypes in CRC bulk transcriptomic data. The ssGSEA and CIBERSORT algorithms were used to evaluate the relative infiltration levels of different cell types in the tumor microenvironment (TME). Single-cell transcriptomic analysis was performed to confirm classification related to NRGs. NRG_score was developed to predict patients' survival outcomes with low-throughput validation in a patients' cohort from Fudan University Shanghai Cancer Center. RESULTS: We identified three distinct necroptosis-related classifications (NRCs) with discrepant clinical outcomes and biological functions. Characterization of TME revealed that there were two stable necroptosis-related phenotypes in CRC: a phenotype characterized by few TME cells infiltration but with EMT/TGF-pathways activation, and another phenotype recognized as immune-excluded. NRG_score for predicting survival outcomes was established and its predictive capability was verified. In addition, we found NRCs and NRG_score could be used for patient or drug selection when considering immunotherapy and chemotherapy. CONCLUSIONS...