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Peer-reviewedCC BY 4.0PLOS One

The role of insulin resistance in the development of hepatocellular carcinoma with computational analysis of IRS-1 interaction with HCV genotype 3 core protein

  • Dr Tufael1
  • Mohd Hasan Mujahid2
  • Most Farhana Akter3
  • Tahsin Salam4
  • Md Abu Bakar Siddique5
  • Kaniz Fatima Bari6
  • Asim Debnath7
  • Nabil Deb Nath8
8 affiliations
  1. 1Department of Biochemistry, Parul University, Vadodara, Gujarat, India
  2. 2Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, Uttarakhand, India
  3. 3Botany Section, School of Sciences, Maulana Azad National Urdu University, Hyderabad, Telangana, India
  4. 4Department of Pharmacy, University of Development Alternative, Dhaka, Bangladesh
  5. 5Internal Medicine and Critical Care Medicine, United Medical College Hospital, Dhaka, Bangladesh
  6. 6Department of Biological Sciences, St John’s University, New York, United States of America
  7. 7Department of Biochemistry, Shaphena Women’s Dental College, Dhaka, Bangladesh
  8. 8Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida, United States of America
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Abstract

The link between insulin resistance (IR) and hepatocellular carcinoma (HCC), especially in relation to HCV genotype-3 infection, is still poorly understood. In South Asian countries and among the peoples of the United States, this problem remains a major public health concern. According to previous studies, metabolic and viral interactomes have not been analyzed together, and hence this is a limitation of the study. This cross-sectional observational study involved 110 people, categorized into control (n=20), chronic hepatitis C (CHC) (n=45), and hepatocellular carcinoma (HCC) (n=45) groups. Clinical, biochemical, and metabolic parameters-HOMA-IR and HbA1c-were measured. The appropriate statistical tests were used for group comparisons. We performed molecular docking to investigate the interaction between the HCV genotype-3 core protein and human IRS-1 using ClusPro. HCC was independently associated with stage III-V fibrosis (AOR: 24.18), elevated HOMA-IR >4, a key indicator of insulin resistance (AOR: 3.53), and AFP >10 ng/mL (AOR: 3.71). Moreover, HbA1c >7% greater GGT and low albumin level were significantly higher in HCC group (P<0.05). Obese patients had higher IR markers, but CHC-to-HCC progression depended more on combined fibrosis and metabolic dysregulation than obesity alone. Docking analysis, there was a strong hydrophobic and electrostatic interaction between HCV core protein and IRS-1, with a binding energy of -1196.0 kcal/mol, indicating a strong and stable interaction between the two proteins. According to this study, it is possible that the presence of insulin resistance, advanced fibrosis, and viral persistence may interact biochemically and molecularly to contribute to hepatocellular carcinoma in cases of HCV genotype-3 infection.

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Cite

BibTeXRIS
BibTeX
@article{tufael2026role,
  title = {{The role of insulin resistance in the development of hepatocellular carcinoma with computational analysis of IRS-1 interaction with HCV genotype 3 core protein}},
  author = {Dr Tufael and Mohd Hasan Mujahid and Most Farhana Akter and Tahsin Salam and Md Abu Bakar Siddique and Kaniz Fatima Bari and Asim Debnath and Nabil Deb Nath},
  journal = {PLOS One},
  year = {2026},
  month = sep,
  doi = {10.1371/journal.pone.0358858},
  url = {https://doi.org/10.1371/journal.pone.0358858},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - The role of insulin resistance in the development of hepatocellular carcinoma with computational analysis of IRS-1 interaction with HCV genotype 3 core protein
AU  - Dr Tufael
AU  - Mohd Hasan Mujahid
AU  - Most Farhana Akter
AU  - Tahsin Salam
AU  - Md Abu Bakar Siddique
AU  - Kaniz Fatima Bari
AU  - Asim Debnath
AU  - Nabil Deb Nath
PY  - 2026
DA  - 2026/09/25
JO  - PLOS One
DO  - 10.1371/journal.pone.0358858
UR  - https://doi.org/10.1371/journal.pone.0358858
AB  - The link between insulin resistance (IR) and hepatocellular carcinoma (HCC), especially in relation to HCV genotype-3 infection, is still poorly understood. In South Asian countries and among the peoples of the United States, this problem remains a major public health concern. According to previous studies, metabolic and viral interactomes have not been analyzed together, and hence this is a limitation of the study. This cross-sectional observational study involved 110 people, categorized into control (n=20), chronic hepatitis C (CHC) (n=45), and hepatocellular carcinoma (HCC) (n=45) groups. Clinical, biochemical, and metabolic parameters-HOMA-IR and HbA1c-were measured. The appropriate statistical tests were used for group comparisons. We performed molecular docking to investigate the interaction between the HCV genotype-3 core protein and human IRS-1 using ClusPro. HCC was independently associated with stage III-V fibrosis (AOR: 24.18), elevated HOMA-IR >4, a key indicator of insulin resistance (AOR: 3.53), and AFP >10 ng/mL (AOR: 3.71). Moreover, HbA1c >7% greater GGT and low albumin level were significantly higher in HCC group (P<0.05). Obese patients had higher IR markers, but CHC-to-HCC progression depended more on combined fibrosis and metabolic dysregulation than obesity alone. Docking analysis, there was a strong hydrophobic and electrostatic interaction between HCV core protein and IRS-1, with a binding energy of -1196.0 kcal/mol, indicating a strong and stable interaction between the two proteins. According to this study, it is possible that the presence of insulin resistance, advanced fibrosis, and viral persistence may interact biochemically and molecularly to contribute to hepatocellular carcinoma in cases of HCV genotype-3 infection.
SN  - 1932-6203
ER  -