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Peer-reviewedCC BY 4.0PLOS One

Commonly expressed key driver genes in the pathogenesis of viral and non-viral liver cancer

  • Melika Zamanian1
  • Niloofar Bajool2
  • Yasamin Haghir-Sharif-Zamini3
  • Seyedeh-Sanaz Araban4
  • Farbod Nassiri5
  • Seyedeh-Nasim Mirbahari6
  • Rayhaneh Ahangar-Parvin7
  • Roshanak Shams8
  • Massoud Vosough
  • Sara Taleahmad
8 affiliations
  1. 1Department of Applied Cell Sciences, Faculty of Basic Sciences and Advanced Medical Technologies, Royan Institute, ACECR, Tehran, Iran
  2. 2Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  3. 3Department of Cell and Developmental Biology, Faculty of Basic Sciences and Advanced Technologies in Medicine, University of Science and Culture, Tehran, Iran
  4. 4Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  5. 5Department of Tissue Engineering, Faculty of Basic Sciences and Advanced Technologies in Medicine, Royan Institute, ACECR, Tehran, Iran
  6. 6Department of Cell Engineering, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
  7. 7Bone and Joint Reconstruction Research Center, Department of Orthopedics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
  8. 8Experimental Cancer Medicine, Institution for Laboratory Medicine, Karolinska Institute, Stockholm, Sweden
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Abstract

Background: Hepatocellular carcinoma (HCC) is a common and lethal liver cancer primarily associated with viral infections like hepatitis B virus (HBV) and hepatitis C virus (HCV), as well as non-viral causes. Understanding the molecular mechanisms of these subtypes is essential for identifying potential biomarkers and therapeutic targets. Methods: In this study, an integrated bioinformatics approach was used to analyze publicly available datasets related to HBV-associated, HCV-associated, and non-viral HCC. Functional enrichment analyses and protein–protein interaction (PPI) networks were constructed to identify key hub genes. Results: Our analysis identified dysregulated genes across all HCC subtypes. Among these, GPC3 and SPARCL1 were significantly upregulated, while ALB and HNF4α were downregulated, and are involved in critical cancer pathways such as Wnt, PI3K/Akt, and p53 signaling. Functional analysis linked these DEGs to essential processes in tumorigenesis, including cell cycle regulation and immune modulation. Notably, SPARCL1 has been identified as a potential inhibitor of SPP1, a key driver of HCC. Validation using databases such as GEPIA and TNMplot confirmed the dysregulation of these genes in numerous HCC tissue samples and their significant association with patient prognosis. Conclusion: This study provides a comprehensive overview of HCC pathogenesis by suggesting a shared gene profile between viral and non-viral forms, paving the way for universal diagnostic markers and targeted therapies while highlighting the need for further experimental validation to advance precision medicine in HCC.

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Cite

BibTeXRIS
BibTeX
@article{zamanian2026commonly,
  title = {{Commonly expressed key driver genes in the pathogenesis of viral and non-viral liver cancer}},
  author = {Melika Zamanian and Niloofar Bajool and Yasamin Haghir-Sharif-Zamini and Seyedeh-Sanaz Araban and Farbod Nassiri and Seyedeh-Nasim Mirbahari and Rayhaneh Ahangar-Parvin and Roshanak Shams and Massoud Vosough and Sara Taleahmad},
  journal = {PLOS One},
  year = {2026},
  month = nov,
  doi = {10.1371/journal.pone.0349647},
  url = {https://doi.org/10.1371/journal.pone.0349647},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Commonly expressed key driver genes in the pathogenesis of viral and non-viral liver cancer
AU  - Melika Zamanian
AU  - Niloofar Bajool
AU  - Yasamin Haghir-Sharif-Zamini
AU  - Seyedeh-Sanaz Araban
AU  - Farbod Nassiri
AU  - Seyedeh-Nasim Mirbahari
AU  - Rayhaneh Ahangar-Parvin
AU  - Roshanak Shams
AU  - Massoud Vosough
AU  - Sara Taleahmad
PY  - 2026
DA  - 2026/11/06
JO  - PLOS One
DO  - 10.1371/journal.pone.0349647
UR  - https://doi.org/10.1371/journal.pone.0349647
AB  - Background: Hepatocellular carcinoma (HCC) is a common and lethal liver cancer primarily associated with viral infections like hepatitis B virus (HBV) and hepatitis C virus (HCV), as well as non-viral causes. Understanding the molecular mechanisms of these subtypes is essential for identifying potential biomarkers and therapeutic targets. Methods: In this study, an integrated bioinformatics approach was used to analyze publicly available datasets related to HBV-associated, HCV-associated, and non-viral HCC. Functional enrichment analyses and protein–protein interaction (PPI) networks were constructed to identify key hub genes. Results: Our analysis identified dysregulated genes across all HCC subtypes. Among these, GPC3 and SPARCL1 were significantly upregulated, while ALB and HNF4α were downregulated, and are involved in critical cancer pathways such as Wnt, PI3K/Akt, and p53 signaling. Functional analysis linked these DEGs to essential processes in tumorigenesis, including cell cycle regulation and immune modulation. Notably, SPARCL1 has been identified as a potential inhibitor of SPP1, a key driver of HCC. Validation using databases such as GEPIA and TNMplot confirmed the dysregulation of these genes in numerous HCC tissue samples and their significant association with patient prognosis. Conclusion: This study provides a comprehensive overview of HCC pathogenesis by suggesting a shared gene profile between viral and non-viral forms, paving the way for universal diagnostic markers and targeted therapies while highlighting the need for further experimental validation to advance precision medicine in HCC.
SN  - 1932-6203
ER  -