The anticancer mechanism of the TOB2 gene in renal clear cell carcinoma and the prediction of potential Chinese medicine targets based on bioinformatic analysis
LIU Jin,YANG Shi-jie,GUO Tie
Department of Urology, The Third Hospital of Hebei Medical University, Shijiazhuang050051, China
Abstract:
Objective To explore the tumor suppressor mechanism of TOB2 gene in clear cell renal cell carcinoma (ccRCC) and predict potential traditional Chinese medicine (TCM) targets by bioinformatics analysis. Methods Gene expression data and clinical information of ccRCC were obtained from public databases. Prognostic analysis was conducted and differentially expressed genes (DEGs) were screened. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using R software packages to analyze the functional pathways of TOB2 gene. The CIBERSORT algorithm was used to analyze immune cell infiltration and explore the correlation between immune cells and TOB2 gene. Potential TCM targets related to TOB2 were retrieved from TCM databases (such as TCMSP and ETCM). Results Bioinformatics analysis revealed that TOB2 gene was lowly expressed in ccRCC and was an independent prognostic factor for overall survival, disease-specific survival, and progression-free survival in ccRCC patients. Its low expression was associated with high tumor invasiveness and poor prognosis. The prognostic model constructed by TOB2 gene could effectively predict patient survival rate. Through functional enrichment analysis, it was found that DEGs between the high and low expression groups of TOB2 might play a role in the pathogenesis of ccRCC through the regulation of the immune microenvironment and lipoproteins. Moreover, low expression of TOB2 significantly enriched biological processes related to lipid droplet accumulation and the MAPK pathway, thereby promoting tumor proliferation and invasion. Immune infiltration analysis showed that there were significant differences in the infiltration levels of 16 types of immune cells between the high and low expression groups of TOB2, and TOB2 expression was correlated with the infiltration levels of multiple immune cells. Additionally, there were significant differences in the expression levels of immune checkpoint-related protein genes between the two groups. Prediction indicated that TCMs such as Hedera helix, Sedum lineare, Vitex negundo, and Saururus chinensis might exert anti-tumor effects by targeting TOB2. Conclusion TOB2 gene is an independent prognostic factor in ccRCC, and its expression level may be closely related to immune cell infiltration and lipid metabolism, suggesting that it may serve as a potential therapeutic target. TCMs such as Hedera helix and Sedum lineare may provide new ideas and potential targets for the treatment of ccRCC by regulating TOB2-related pathways, providing a theoretical basis for the combination of traditional Chinese and Western medicine in the treatment of ccRCC.
