An anoikis-related gene signature predicts prognosis, drug sensitivity, and immune microenvironment in cholangiocarcinoma

Background: Cholangiocarcinoma is a malignant invasive biliary tract carcinoma with a poor prognosis. Anoikis-related genes are prognostic features of a variety of cancers. However, the value of prognostication and therapeutic effect of anoikis-related genes in cholangiocarcinoma have not been reported. The aim of this research was developing an ARGs signature associated with cholangiocarcinoma patients. Methods: We introduced transcriptome data to discover genes that were differentially expressed in cholangiocarcinoma. Subsequently, WGCNA was utilized to screen critical module genes in reference to anoikis. The univariate Cox, Lasso regression and Kaplan-Meier survival were executed to build a prognostic signature. We further performed gene functional enrichment, immune microenvironment and immunotherapy analysis between two risk subgroups. Finally, the pRRophetic algorithm was applied to compare the half inhibitory concentration value of several drugs. Results: A grand total of 1844 genes with differential expression related to the cholangiocarcinoma patients were identified. Furthermore, we obtained 2678 key module genes related to anoikis. Then, a prognostic signature was developed using the 6 prognostic genes (FXYD2, PCBD1, C1RL, GMNN, LAMA4 and HACL1). Independent prognostic analysis showed that risk score and alcohol could function as separate prognostic variables. We found cetain distinction in the immune microenvironment between the two risk subgroups. Moreover, immunotherapy evaluation showed that the anoikis-related gene signature could be applied as a therapy predictor. Finally, Chemotherapeutic drug sensitivity results showed that the low-risk group responded better to bosutinib, gefitinib, gemcitabine, and paclitaxel, while the high-risk group responded better to axitinib, cisplatin, and imatinib. Conclusion: The prognostic signature comprised of FXYD2, PCBD1, C1RL, GMNN, LAMA4 and HACL1 based on anoikis-related genes was established, which provided theoretical basis and reference value for the research and treatment of cholangiocarcinoma.