SOCS2 serves as a prognostic indicator and is regulated by miR-7-5p in hepatocellular carcinoma

Background Suppressor of cytokine signaling (SOCS) family members are essential components of negative regulation of cytokine signaling known to be involved in occurrence and progression of hepatocellular carcinoma (HCC), while a comprehensive analysis of the correlation between SOCS family members and HCC has not yet been elucidated. Methods Differential expression analysis of SOCS genes was performed on TIMER, which was further validated by GSE94660 dataset from Gene Expression Omnibus (GEO). Prognostic values of SOCS genes were analyzed by TIMER and GEPIA. TISIDB was used to assess association between SOCS2 expression, clinical stages and pathological grades of HCC, as well as SOCS2 expression across immune subtypes and iClusters. Differential expression of genes (DEGs) identification was tested by two-tail student’s t test using The Cancer Genome Atlas (TCGA) RNA-seq of HCC. And functional annotation of the DEGs was performed by Metascape. Fraction of Immune cells was estimated by CIBERSORT, and infiltration difference were compared by two-tail student’s t test. Genetic alteration identification and promoter methylation evaluation were analyzed by cBioPortal and DNMIVD, respectively. Starbase was used to predict potential miRNAs that target SOCS2. Differential expressions of candidate miRNAs were analyzed by dbMEMC, which was further validated by GSE22058 from GEO. Survival analysis of miRNA was performed with KM Plotter. Results Differential expression analysis showed SOCS2 and SOCS3 were significantly downregulated, while SOCS5 and SOCS7 were upregulated in HCC. Survival analysis revealed only SOCS2 mRNA had significant prognostic value in terms of overall survival and disease-free survival in HCC. Specifically, higher SOCS2 predicted improved outcome. Significant correlations were found between SOCS2 and pathological stage, grade, molecular subtypes and immune subtypes. When comparing SOCS2high versus SOCS2low patients, the DEGs were functionally enriched in metabolism of RNA, organic cyclic compound catabolic process, and rRNA processing in the nucleus and cytosol. Immune cell infiltration analysis showed resting memory CD4 T cells, γδ T cells, follicular helper T cells, regulatory T cells and M0 macrophages were associated with SOCS2 expression. Mechanistically, miR-7-5p was the potential contributor responsible for downregulation of SOCS2. Conclusions SOCS2 could be a promising prognostic indicator and a potential therapeutic target for HCC.