• TGF-β rs9282871 TT genotype linked to high HCC susceptibility. • Serum TGF-β was markedly elevated in hepatocellular carcinoma patients. • miR-let-7c expression was significantly downregulated in HCC cases. • Inverse correlation between TGF-β levels and miR-let-7c expression. • TGF-β and miR-let-7c serve as potential diagnostic HCC biomarkers. Hepatocellular carcinoma (HCC) is ranked globally as the second most common cancer-related death. Transforming growth factor beta (TGF-β) plays a dual role in HCC. Meanwhile, miR-let-7c has been identified as a tumor suppressor microRNA that regulates oncogenic pathways, including the TGF-β signaling cascade. Dysregulation of miR-let-7c may enhance TGF-β1 overproduction, sustaining oncogenic signaling and accelerating HCC progression. To investigate the impact of TGF-β gene variants and the relative expression of miR-let-7c on TGF-β production in HCC patients. A total of 150 HCC patients and 50 healthy controls were enrolled. DNA was extracted for TGF-β genotyping, serum TGF-β1 levels were quantified using an ELISA assay, and miR-let-7c expression was assessed by quantitative real-time PCR (qRT-PCR). In silico analysis was performed to confirm interactions. Our results revealed that HCC patients had TT genotype (59%), while the control group TT genotype represents (16%,) with high significance differences between control and HCC patients (P = 0.0001). TGF-β was significantly elevated in the HCC group (366 ± 111.8 pg/mL) versus controls (100 ± 26.57 pg/mL, P < 0.0001). The relative expression of circulating miR-let-7c was significantly downregulated in HCC patients compared to the control group (P = 0.0001). TGF-β demonstrated high diagnostic accuracy (AUC = 0.9907, P = 0.0001). While miR-let7c showed AUC = 0.7172, P = 0.0001. Our results showed that TGF-β genotypes are significantly associated with increased serum TGF-β protein levels (P < 0.0001) and reduced miR-let-7c serum levels (P < 0.0001). Bioinformatics tools confirmed that miR-let7c targets the TGF-β pathway, supporting its regulatory role. TGF-β rs 9282871 affects TGF-β production in HCC patients. The T allele, TT genotype, and downregulation of miR-let-7c activate the TGF-β pathway. Both TGF-β protein and let-7c expression can be diagnostic biomarkers of HCC. the TT genotype of the TGF-β gene can be used as a genetic biomarker for disease progression and outcome.
Farouk et al. (Sun,) studied this question.