Prognostic and Predictive Values of MAD2L1 in Cholangiocarcinoma

Abstract

Background: This study aimed to investigate the expression of Mitotic arrest deficient 2-like protein 1 (MAD2L1) in cholangiocarcinoma (CCA) and its biological function. Methods: Our study performed bioinformatics to analyze the microarray data from the Gene Expression Omnibus (GEO) database and obtained the differentially expressed genes (DEGs). Enrichment assay and protein-protein interaction networks analysis were conducted to extract hub genes. Mitotic arrest deficient 2-like protein 1 (MAD2L1) was investigated in tumor and adjacent nonneoplastic biliary ducts in 42 samples by immunohistochemistry. Subsequently, MAD2L1 was manipulated, and its function was examined in CCA cell lines and in vivo model. Results: 297 DEGs were extracted from the microarray data. And seven hub genes were defined through the enrichment assay and protein-protein interaction networks analysis. MAD2L1 was picked up as a novel biomarker, according to hierarchical cluster analysis and Kaplan-Meier survival analysis. MAD2L1 was specifically expressed in cancer tissues but not in the surrounding normal tissue, and 31 (73.81%) of 42 CCAs were MAD2L1 positive by immunohistochemistry. MAD2L1 expression was significantly correlated with tumor size, pathological grade, and clinical stage. Kaplan-Meier analysis demonstrated an inverse correlation between MAD2L1 expression and overall survival. Real-time polymerase chain reaction (RT-PCR) and Immunoblotting results further confirmed the results of immunohistochemistry and bioinformatic analysis from the database. In vitro and in vivo models, decreasing MAD2L1 could significantly suppress tumor growth.Conclusion: High MAD2L1 expression predicts the advanced stage of CCA. Targeting MAD2L1 may be a potential tumor suppressor and may provide the biological basis for a new therapeutic strategy.Trial registration: [2020]KY157-01. Registered 1st April 2020 - Retrospectively registered, http://114.255.48.20/login#.