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Bulk and single-cell transcriptome profiling reveal necroptosis-based molecular classification, tumor microenvironment infiltration characterization, and prognosis prediction in colorectal cancer.
Luo, Wenqin; Xiang, Wenqiang; Gan, Lu; Che, Ji; Li, Jing; Wang, Yichao; Han, Lingyu; Gu, Ruiqi; Ye, Li; Wang, Renjie; Zhang, Xiuping; Xu, Ye; Dai, Weixing; Mo, Shaobo; Li, Qingguo; Cai, Guoxiang.
Afiliação
  • Luo W; Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Xiang W; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • Gan L; Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Che J; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • Li J; Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Wang Y; Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Han L; Department of Center of Evidence-Based Medicine, Fudan University, Shanghai, China.
  • Gu R; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • Ye L; Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Wang R; Department of CyberKnife Center, Huashan Hospital, Fudan University, Shanghai, China.
  • Zhang X; Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Xu Y; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • Dai W; Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Mo S; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
  • Li Q; Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
  • Cai G; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
J Transl Med ; 20(1): 235, 2022 05 19.
Article em En | MEDLINE | ID: mdl-35590418
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Microambiente Tumoral Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: Asia Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Microambiente Tumoral Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Humans País/Região como assunto: Asia Idioma: En Ano de publicação: 2022 Tipo de documento: Article