DOI: 10.4103/bbrj.bbrj_110_26 ISSN: 2588-9834

Clinical and In silico Evaluation of Cholesterol and Triglyceride Dysregulation and Its Regulatory Targets in Hepatocellular Carcinoma Patients with Metabolic Disorders

Abbas Kadhim Jiheel Al-Hameedawi, Ibrahim Majer Mohammed, Mohammed J. Al-Yasiri, Adnan Jassim Mohammed Al-Fartosy
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Abstract

Background:

Metabolic alterations in hepatocellular carcinoma (HCC) focus on lipid pathway disruption, driving tumor proliferation and immune evasion alongside demographic risk factors via specific genetic and enzymatic targets. The significance of total cholesterol (TC) and triglyceride (TG) levels in HCC patients with metabolic disorders in Maysan, Iraq, considering patient sex and residence area.

Methods:

This study analyzed 510 participants (255 HCC patients with metabolic disorders and 255 healthy controls) using serum measurements of TC and TG levels, logistic regression, Analysis of Variance (ANOVA), and AutoDock Vina molecular docking simulations for Atorvastatin, Rutin, Orlistat, Avasimibe, and Cholic Acid.

Results:

Elevated TG levels correlated with increased HCC risk (odds ratio [OR] =1.082, P < 0.001), while higher TC levels were inversely related (OR = 0.966, P < 0.001), highlighting peripheral “cholesterol trapping.” Three-Way ANOVA showed lipid alterations were associated with disease status ( P = 0.001) but did not vary by sex or residence ( P = 0.901). Preliminary docking results identified Atorvastatin as the strongest, redocking-validated binder, with Rutin a closely comparable candidate meriting further exploration; Cholic Acid’s predicted binding could not be similarly validated.

Conclusion:

A reliable, demographically stable biomarker for HCC is peripheral dyslipidemia. Although extrapolation to cholic acid or clinical application awaits additional validation, Rutin’s binding design suggests it may be worthy of further research for regulating lipid pathways in HCC.

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