Co-expression network analysis revealed ATP۶AP۱-DT, andTRIM۵۲-AS۱ as potential therapeutic lncRNAs in hepatocellular carcinoma

Liver hepatocellular carcinoma (LIHC) is the fourth most common cancer-related cause of death globally, with the sixth highest incidence of new occurrences. Fibroblast growth factor receptor ۴ (FGFR۴) is a receptor tyrosine kinase and its aberrant activation is one of the carcinogenic factors in Hepatocellular carcinoma. In this study, we used differential expression and co-expression analyses to discover new therapeutic targets in LIHC based on FGFR۴ gene expression. Methods:The expression profile of LIHC primary tumor and normal tissue were downloaded from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database, respectively. Differential expression analysis was performed using the DESeq۲ package (۱.۳۶) in R (۴.۲.۱). | log۲FC|۰.۵۸, and adjusted p-value< ۰.۰۵ cuto↵ were set to identify the significant differentially expressed genes. The weighted gene co-expression network analysis (WGCNA) package (۱.۷۱) was used to construct the co-expression modules. The module containing the FGFR۴ gene was identified and significantly differentially expressed long non-coding RNAs (lncRNAs) co-expressed with FGFR۴ were visualized with Cytoscape software (۳.۹.۱). Finally, survival analysis was performed using the Survival Genie web platform. Results:A total of ۱۱۲۰۶ genes were significantly differentially expressed in LIHC samples compared to normal samples. ۱۶ modules were identified, among which the brown module contains the FGFR۴ gene. Three lncRNAs including ATP۶AP۱ Divergent Transcript (ATP۶AP۱-DT), TRIM۵۲ Antisense RNA ۱ (TRIM۵۲-AS۱), and ZSCAN۱۶ Antisense RNA ۱ (ZSCAN۱۶-AS۱) were significantly upregulated in LIHC and were co-expressed with FGFR۴. The survival analysis indicates that the overexpression of FGFR۴, ATP۶AP۱-DT, and TRIM۵۲-AS۱ is significantly correlated to lower overall survival in LIHC patients.Conclusion:In conclusion, our analysis identifies potential therapeutic targets in FGFR۴ signaling which may contribute to LIHC progression and lower overall survival.

کلیدواژه ها:

LIHC ، FGFR۴ ، Co-expression ، WGCNA