The HCV-Melanoma Paradox: First Multi-Cohort and Molecular Net-Work Analysis Reveals Lower Incidence but Worse Outcomes—Integrating Clinical, Real-World, and In Silico Data
Essam Al Ageeli,
Jawaher A. Abdulhakim,
Mohammad H. Hussein,
Maryam M. Alnoman,
Samia S. Alkhalil,
Peter P. Issa,
Nader A. Nemr,
Ahmed Abdelmaksoud,
Dhaifallah A. Alenizi,
Manal S. Fawzy,
Eman A. Toraih
Affiliations
Essam Al Ageeli
Department of Basic Medical Sciences, Faculty of Medicine, Jazan University, Jazan 45141, Saudi Arabia
Jawaher A. Abdulhakim
Department of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu 46423, Saudi Arabia
Mohammad H. Hussein
Ochsner Clinic Foundation, New Orleans, LA 70121, USA
Maryam M. Alnoman
Department of Biology, Faculty of Science, Taibah University, Yanbu 46423, Saudi Arabia
Samia S. Alkhalil
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Alquwayiyah 11961, Saudi Arabia
Peter P. Issa
School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
Nader A. Nemr
Endemic and Infectious Diseases Department, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
Ahmed Abdelmaksoud
Department of Internal Medicine, University of California, Riverside, CA 92521, USA
Dhaifallah A. Alenizi
Department of Medicine, Faculty of Medicine, Northern Border University, Arar 91431, Saudi Arabia
Manal S. Fawzy
Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar 1321, Saudi Arabia
Eman A. Toraih
Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, USA
Background and Objectives: The relationship between hepatitis C virus (HCV) infection and melanoma remains poorly understood. This study aimed to investigate the association between HCV and melanoma, assess outcomes in patients with both conditions, and explore potential molecular mechanisms connecting the two diseases. Materials and Methods: We conducted a retrospective cohort study of 142 melanoma patients, including 29 with HCV-related cirrhosis, and analyzed their clinical outcomes. For external validation, we used the TriNetX Global Collaborative Network database, comprising 219,960 propensity-matched patients per group. An in silico analysis was performed to identify the molecular pathways linking HCV and melanoma. Results: In the retrospective cohort, HCV-positive melanoma patients showed an increased risk of early relapse (41.4% vs. 18.6%, p = 0.014), recurrence (65.5% vs. 39.8%, p = 0.020), and mortality (65.5% vs. 23.0%, p p p Conclusions: While HCV infection may be associated with a lower risk of melanoma development, HCV-positive patients who develop melanoma have poorer outcomes. The identified molecular pathways provide potential targets for future research and therapeutic interventions.
