Integrated expression profiling reveals molecular crosstalk between CFTR, FASN, FRAP (mTOR), and BANK1 in hepatocellular carcinoma

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.

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Journal
Scientific Reports
Published
2026-09-15
DOI
https://doi.org/10.1038/s41598-026-71100-5
Primary Topic
Cancer, Lipids, and Metabolism
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article
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article

Integrated expression profiling reveals molecular crosstalk between CFTR, FASN, FRAP (mTOR), and BANK1 in hepatocellular carcinoma

Fizzah Abid, Hafsa Aziz, Janeen H. Trembley, Sadia Fatima et al.
Scientific Reports
Cancer, Lipids, and Metabolism
article

Integrated expression profiling reveals molecular crosstalk between CFTR, FASN, FRAP (mTOR), and BANK1 in hepatocellular carcinoma

Fizzah Abid, Hafsa Aziz, Janeen H. Trembley, Sadia Fatima, Seyyedha Abbas, Suhail Razak, Rubina Nazli, Tayyaba Afsar, Ali Abusharha, Tahir Mehmood
article en

Abstract

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.

Scientific ReportsVol. 16(1)
University of Minnesota (US), Pakistan Atomic Energy Commission (PK), Khyber Medical University (PK), King Saud University (SA), Minneapolis VA Health Care System (US), University of Minnesota Medical Center (US), Bahria University (PK), National University of Sciences and Technology (PK)
Reduced inequalities
Openalex Percentile: Top 14%
Cancer, Lipids, and Metabolism
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