Identification of a necroptosis-related gene signature as a novel prognostic biomarker of cholangiocarcinoma.

Background: Cholangiocarcinoma (CHOL) is the most prevalent type of malignancy and the second most common form of primary liver cancer, resulting in high rates of morbidity and mortality. Necroptosis is a type of regulated cell death that appears to be involved in the regulation of several aspects of cancer biology, including tumorigenesis, metastasis, and cancer immunity. This study aimed to construct a necroptosis-related gene (NRG) signature to investigate the prognosis of CHOL patients using an integrated bioinformatics analysis. Methods: CHOL patient data were acquired from the Gene Expression Omnibus (GEO) (GSE89748, GSE107943) and The Cancer Genome Atlas (TCGA) databases, with NRGs data from the necroptosis pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Univariate and multivariate regression analyses were performed to establish the NRG signatures. Kaplan-Meier (KM) curves were used to evaluate the prognosis of patients with CHOL. Functional enrichment analysis was performed to identify key NRG-associated biological signaling pathways. We also applied integrative multi-omics analysis to the high- and low-risk score groups. Spearman's rank correlation was used to clarify the relationship between the NRG signature and immune infiltration. Results: 65 differentially expressed (DE) NRGs were screened, five of which were selected to establish the prognostic signature of NRG Conclusion: These findings demonstrate that the five-NRG prognostic signature for CHOL patients is reasonably accurate and valid, and it may prove to be of considerable value for the treatment and prognosis of CHOL patients in the future.