Comprehensive analysis of bioinformatics and system biology reveals the association between Girdin and hepatocellular carcinoma

by Tengda Huang, Hongying Chen, Hongyuan Pan, Tian Wu, Xiangyi Ren, Liwen Qin, Kefei Yuan, Fang He

Hepatocellular carcinoma is one of the leading causes of cancer-related mortality worldwide. The actin-binding protein Girdin is overexpressed in various tumors, promoting tumorigenesis and progression. However, the exact mechanisms by which Girdin regulates liver cancer remain poorly understood.

This study comprehensively analyzed the expression level of Girdin in liver cancer and adjacent tissue, along with the correlation between Girdin expression and the clinical characteristics and prognosis of liver cancer. The analysis integrated data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Subsequently, Girdin expression was knocked down to elucidate its role in the progression of liver cancer. Transcriptome sequencing was employed to investigate the mechanistic underpinnings of Girdin’s regulatory impact on liver cancer. Additionally, the Comparative Toxicogenomics Database (CTD) was utilized to identify potential drugs or molecules for liver cancer treatment.

The findings revealed elevated Girdin expression in liver cancer tissues, and heightened Girdin expression correlating with adverse clinical features and prognosis. Silencing of Girdin markedly impeded the proliferation and migration of hepatocellular carcinoma cells. Moreover, transcriptome sequencing demonstrated that silencing Girdin led to differential expression of 176 genes and inhibition of the PI3K/Akt signaling pathway, as well as its upstream pathways—Cytokine-cytokine receptor interaction and Chemokine signaling pathway. Ultimately, we propose that Imatinib Mesylate, Orantinib, Resveratrol, Sorafenib, and Curcumin may interact with Girdin, potentially contributing to the treatment of liver cancer.

This study reveals the association between Girdin and hepatocellular carcinoma, providing novel clues for future research and treatment of hepatocellular carcinoma.