Deciphering a cell death-associated signature for predicting prognosis and response to immunotherapy in lung squamous cell carcinoma

Autor: Guangxian Mao, Dongyong Yang, Bin Liu, Yu Zhang, Sijia Ma, Shang Dai, Guoqiang Wang, Wenxiang Tang, Huafei Lu, Shangli Cai, Jialiang Zhu, Huaping Yang
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Respiratory Research, Vol 24, Iss 1, Pp 1-14 (2023)
Druh dokumentu: article
ISSN: 1465-993X
DOI: 10.1186/s12931-023-02402-9
Popis: Abstract Background Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell carcinoma, accounting for about 30% of all lung cancers. Yet, the evaluation of prognostic outcome and therapy response of patients with LUSC remains to be resolved. This study aimed to explore the prognostic value of cell death pathways and develop a cell death-associated signature for predicting prognosis and guiding treatment in LUSC. Methods Transcriptome profiles and corresponding clinical information of LUSC patients were gathered from The Cancer Genome Atlas (TCGA-LUSC, n = 493) and Gene Expression Omnibus database (GSE74777, n = 107). The cell death-related genes including autophagy (n = 348), apoptosis (n = 163), and necrosis (n = 166) were retrieved from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. In the training cohort (TCGA-LUSC), LASSO Cox regression was used to construct four prognostic signatures of respective autophagy, apoptosis, and necrosis pathway and genes of three pathways. After comparing the four signatures, the cell death index (CDI), the signature of combined genes, was further validated in the GSE74777 dataset. We also investigated the clinical significance of the CDI signature in predicting the immunotherapeutic response of LUSC patients. Results The CDI signature was significantly associated with the overall survival of LUSC patients in the training cohort (HR, 2.13; 95% CI, 1.62‒2.82; P
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