Seyyedha Abbas, Fizzah Abid, Tahir Mehmood, Sadia Fatima, Janeen H Trembley, Rubina Nazli, Hafsa Aziz, Ali Abusharha, Tayyaba Afsar, Suhail Razak
Hepatocellular carcinoma (HCC) is a common malignancy characterised by molecular heterogeneity and poor prognosis. The purpose of this study was to determine differences in the expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), Fatty Acid Synthase (FASN), FKBP12-rapamycin-associated protein (FRAP; mTOR), and B-cell scaffold protein with ankyrin repeats 1 (BANK1) between HCC patients and controls. A total of 200 blood samples (100 from HCC patients and 100 from controls) were analysed using Reverse Transcription Polymerase Chain Reaction (RT-PCR), with Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) used as an internal control. The results demonstrated significant upregulation of FASN and FRAP (mTOR) (p < 0.0001) and downregulation of CFTR and BANK1 (p < 0.0001), suggesting potential oncogenic and tumour-suppressive roles, respectively. Gene expression levels also differed significantly across Stages I, II, III, and IV. The Ct values for BANK1 were higher than those for CFTR, FASN, and FRAP (mTOR). Because the expression measurements for the four genes were obtained from blood rather than tumour parenchyma, these findings were not interpreted as direct evidence of gene expression within tumour tissue. Survival analysis using a public dataset revealed that dysregulation of these genes was associated with lower survival rates. In silico pathway analysis demonstrated complex interactions among the four genes, linking them to metabolic regulation, immune signalling, and cellular proliferation pathways. Overall, the integrated network involving CFTR, FASN, FRAP (mTOR), and BANK1 may have potential as a novel prognostic marker by reflecting combined metabolic and immune pathway activity. A combined four-gene logistic regression model demonstrated promising discriminative performance in the present cohort (AUC = 0.89). However, this finding requires validation in independent cohorts before any diagnostic application can be considered.