Document Type
Article
Publication Title
Plasma Proteomic Profiling Reveals Distinct Protein Signatures Associated With Hepatocellular Carcinoma In Chronic Hepatitis B Infection
Abstract
Background
Chronic hepatitis B virus (HBV) infection is a leading cause of hepatocellular carcinoma (HCC), yet reliable biomarkers for early detection and risk stratification remain limited. This study aimed to identify plasma proteins associated with disease progression from chronic HBV infection to HCC.
Methods
Plasma proteomic profiling was conducted using high-resolution LC–MS/MS on samples from healthy controls, chronic HBV carriers, patients with cirrhosis, and individuals with HBV-associated HCC. Differentially expressed proteins were identified through bioinformatics analysis, and protein–protein interaction networks were reconstructed to assess functional relevance.
Results
Eight proteins displayed distinct, stage-specific expression patterns along the disease continuum. ICAM1, TIMP1, and IGFBP7 were progressively upregulated, reflecting roles in inflammation, fibrosis, and tumorigenesis. In contrast, PF4V1 and GPLD1 were downregulated, suggesting loss of protective functions during disease progression. PFN1, TUBA1B, and MDH1 exhibited dynamic modulation linked to cytoskeletal remodeling, cell division, and metabolic reprogramming. Network analysis revealed their involvement in pathways critical for immune regulation, extracellular matrix remodeling, and angiogenesis. Random forest modeling further confirmed their strong discriminatory potential for disease staging.
Conclusion
This study identifies a panel of plasma proteins closely associated with HBV-related HCC progression. These biomarkers may facilitate early detection, improve risk stratification in HBV-infected individuals, and provide new insights into the molecular mechanisms driving liver cancer development.
First Page
Introduction Liver cancer ranks as the sixth most commonly diagnosed cancers worldwide, with an estimated 865,000 new cases reported in 2022. It is the third leading cause of cancer-related mortality, responsible for approximately 757,948 deaths in the same year [1]. The global incidence and mortality of liver cancer are two- to threefold higher in men than in women [2]. Among primary hepatic malignancies, hepatocellular carcinoma (HCC) is the predominant histological subtype and represents a major public health concern due to its skyrocketing incidence and high mortality [2]. HCC typically arises in the context of chronic liver disease, most frequently cirrhosis secondary to chronic viral hepatitis (HBV or HCV), alcohol abuse, or metabolic disorders [3]. In sub-Saharan Africa (SSA), chronic HBV infection remains the principal etiological factor. Importantly, HBV can promote hepato carcinogenesis even in the absence of cirrhosis, largely through integration of viral DNA into the host genome [4]. The global burden of HCC is unevenly distributed, with the highest prevalence in low- and middle-income countries, particularly in SSA and East Asia, where HBV and HCV infections remain endemic [4]. In contrast, metabolic disorders are emerging as dominant risk factors in high-income settings. Projections indicate that liver cancer incidence will rise by approximately 55% by 2040, underscoring the urgent need for improved strategies prevention and early detection [5]. Despite advances in imaging and surveillance, HCC is often diagnosed at advanced stages, where curative interventions such as hepatic resection or liver transplantation are no longer feasible [6]. Current surveillance relies on biannual abdominal ultrasound, often combined with alpha-fetoprotein (AFP) measurement. However, AFP has limited sensitivity for small tumors and may yield false-positive results in benign liver conditions or during pregnancy, reducing its diagnostic reliability [7]. Ultrasound, although widely available, is highly operator dependent and less effective in certain clinical contexts [8]. These limitations hinder early diagnosis and contribute to poor clinical outcomes. To address these challenges, significant efforts have been directed toward the discovery of novel biomarkers for early HCC detection [9]. Proteomic technologies now allow comprehensive profiling of circulating proteins implicated in tumorigenesis [10, 11], and emerging studies have identified candidate serum biomarkers with promising diagnostic utility de [12, 13]. In Burkina Faso, liver cancer ranks tenth and the highest in incidence across African rates [1, 14]. According to 2022 global cancer statistics, it is the leading cause
Last Page
Conclusion Collectively, the proteomic landscape reflective of HBV related liver disease delineated here highlights progressive upregulation of ICAM1, IGFBP7, and TIMP1, progressive downregulation of GPLD1 and PF4V1, and dynamic modulation of PFN1, TUBA1B, and MDH1. This dynamic modulation, highlight key alterations in cytoskeletal structure, cell division, and metabolism during carcinogenesis. These patterns were validated through PPI and Random Forest analyses, which confirmed their discriminatory power and integration into core biological networks relevant to liver disease. In summary, this study provides evidence supporting these proteins as potential biomarkers for early HCC detection and disease monitoring in individuals with HBV infection, particularly in distinguishing cirrhosis from malignant transformation to HCC. Their functional relevance to inflammation, fibrosis, angiogenesis, cytoskeletal remodeling, and metabolic adaptation enhances their utility for both biomarker development and mechanistic insights into HBV-driven hepatocarcinogenesis
DOI
doi: 10.1186/s12014-025-09580-2
Publication Date
1-17-2026
Recommended Citation
Zongo, Sidnooma Véronique; Bauer, Michael A.; Traore, Lassina; Compaore, Tegwinde Rebeca; Yonli, Albert Théophane; Bambara, Augustin Tozoula; Boua, Palwendé Romuald; Sombié, Roger Arsène; Barro, Oumar; Somda, Sosthene K.; Sanou, Mahamoudou; Martinson, Jeremy James; Chamcheu, Jean Christopher; Roberts, Lewis R.; Borad, Mitesh J; Nagalo, Bolni Marius; Tackett, Alan J; Sanou, Adama; Djigma, Florencia Wendkuuni; and Simpore, Jacques, "Plasma Proteomic Profiling Reveals Distinct Protein Signatures Associated With Hepatocellular Carcinoma In Chronic Hepatitis B Infection" (2026). Faculty Publications. 42.
https://digitalcommons.subr.edu/osp_facpubs/42