Expression profile of JAK/STAT signaling pathway genes in hepatitis B virus related hepatocellular carcinoma

Hepatocellular carcinoma (HCC) poses a significant global health burden. Although the JAK/STAT pathway is important in HCC development, its expression patterns remain unclear. This study examined the expression of 76 JAK/STAT pathway-related genes in paired tumour and adjacent non-tumour liver tissues from 32 patients with HBV-associated HCC. Differential expression, co-expression clustering, clinical correlations, and protein-protein interaction network with functional enrichment analyses were conducted. Eight genes were significantly dysregulated in tumour tissues: A2M , GHR , IL6ST , SOCS2 , EGFR , CCND1 , CNTFR were downregulated, while STAT1 was upregulated. The PPI network has identified STAT1 as a central hub, with key interactions involving EGFR , SOCS2 , and IL6ST . Co-expression analysis revealed ten gene clusters, linked to immune regulation, proliferative, and metabolic functions. Immune-related genes in Clusters 2 and 3 (e.g., TSLP , SMAD1 , and STAT4 ) were inversely correlated with bilirubin levels, whereas proliferative/metabolic genes in Cluster 1 were inversely correlated with tumour volume. EGFR was independently associated with CA19-9, while ISG15 , PTPN1 , PTPN6 were associated with albumin levels. This study identifies transcriptional dysregulation of JAK/STAT pathway-related genes in HBV-associated HCC and highlights genes whose expression is associated with tumour and laboratory characteristics. These findings may provide candidates for further investigation and independent validation as potential biomarkers or therapeutic targets.