UBA3 is a potential diagnostic marker and regulates the proliferation and migration in intrahepatic cholangiocarcinama

Abstract Background: Intrahepatic cholangiocarcinoma (ICC) accounts for about 15% of primary liver cancer, and the incidence rate has been rising in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to find its signature genes. The aim of this study is to investigate the relationship between ICC signature genes and its proliferation, invasion and migration. Methods: We screened the ICC dataset from GEO and analyzed the differentially expressed genes (DEGs). Functional enrichment analysis was performed on these DEGs. Weighted gene expression network analysis (WCGNA) was used to screen for key modules. Then, LASSO, SVM-RFE and Random forest analysis were applied to identify the signature genes. Gene set enrichment analysis (GSEA) was then used to explore the signaling pathways associated with the central genes. Finally, cell viability, invasion and migration were assessed using CCK8, wound healing, transwell and western blotting. Results: A total of 781 DEGs were screened from GSE33327 by WGCNA clustering into 9 modules, with the Magenta module (cor= -0.38, p<0.0001) and Midnightbluem module (cor=0.35, p<0.0001) effects significantly correlated with ICC. LASSO, SVM-RFE and Random forest were used to algorithmically select the trait genes, including TOM1 and UBA3. The receiver operating characteristics curve (ROC) for these trait genes was 0.725 and 0.755, respectively, and TOM1 (p>0.05) was therefore discarded in the rank sum test. GSEA analysis showed a positive correlation between UBA3 and MAPK signaling pathway, which was validated by correlation experiments. Conclusions: UBA3 has been screened by bioinformatics methods for the early diagnosis of ICC. In addition, we also explored the effect of UBA3 knockdown on the proliferation and migration of ICC through MAPK signaling pathways. UBA3 provides a new perspective for the study of ICC.