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Journal of Translational Medicine
Published in: Journal of Translational Medicine 1/2022

Open Access 01-12-2022 | Colorectal Cancer | Research

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

Authors: 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

Published in: Journal of Translational Medicine | Issue 1/2022

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Abstract

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

Based on comprehensive analysis, we revealed the potential roles of NRGs in the TME, and their correlations with clinicopathological parameters and patients’ prognosis in CRC. These findings could enhance our understanding of the biological functions of necroptosis, which thus may aid in prognosis prediction, drug selection, and therapeutics development.
Appendix
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Metadata
Title
Bulk and single-cell transcriptome profiling reveal necroptosis-based molecular classification, tumor microenvironment infiltration characterization, and prognosis prediction in colorectal cancer
Authors
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
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Translational Medicine / Issue 1/2022
Electronic ISSN: 1479-5876
DOI
https://doi.org/10.1186/s12967-022-03431-6

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