Genomics & Informatics

Korea Genome Organization (한국유전체학회)
권호 표지
DOI QR코드

DOI QR Code

A genomic and bioinformatic-based approach to identify genetic variants for liver cancer across multiple continents

  • Muhammad Ma'ruf (Faculty of Pharmacy, Universitas Ahmad Dahlan) ;
  • Lalu Muhammad Irham (Faculty of Pharmacy, Universitas Ahmad Dahlan) ;
  • Wirawan Adikusuma (Departement of Pharmacy, University of Muhammadiyah Mataram) ;
  • Made Ary Sarasmita (Department of Clinical Pharmacy, College of Pharmacy, Taipei Medical University) ;
  • Sabiah Khairi (School of Nursing, College of Nursing, Taipei Medical University) ;
  • Barkah Djaka Purwanto (Faculty of Medicine, Universitas Ahmad Dahlan) ;
  • Rockie Chong (Department of Chemistry and Biochemistry, University of California) ;
  • Maulida Mazaya (Research Center for Computing, Research Organization for Electronics and Informatics, National Research and Innovation Agency (BRIN), Cibinong Science Center) ;
  • Lalu Muhammad Harmain Siswanto (Mataram Training Health Center, Indonesia Ministry of Health)
  • Received : 2023.08.14
  • Accepted : 2023.11.30
  • Published : 2023.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Liver cancer is the fourth leading cause of death worldwide. Well-known risk factors include hepatitis B virus and hepatitis C virus, along with exposure to aflatoxins, excessive alcohol consumption, obesity, and type 2 diabetes. Genomic variants play a crucial role in mediating the associations between these risk factors and liver cancer. However, the specific variants involved in this process remain under-explored. This study utilized a bioinformatics approach to identify genetic variants associated with liver cancer from various continents. Single-nucleotide polymorphisms associated with liver cancer were retrieved from the genome-wide association studies catalog. Prioritization was then performed using functional annotation with HaploReg v4.1 and the Ensembl database. The prevalence and allele frequencies of each variant were evaluated using Pearson correlation coefficients. Two variants, rs2294915 and rs2896019, encoded by the PNPLA3 gene, were found to be highly expressed in the liver tissue, as well as in the skin, cell-cultured fibroblasts, and adipose-subcutaneous tissue, all of which contribute to the risk of liver cancer. We further found that these two SNPs (rs2294915 and rs2896019) were positively correlated with the prevalence rate. Positive associations with the prevalence rate were more frequent in East Asian and African populations. We highlight the utility of this population-specific PNPLA3 genetic variant for genetic association studies and for the early prognosis and treatment of liver cancer. This study highlights the potential of integrating genomic databases with bioinformatic analysis to identify genetic variations involved in the pathogenesis of liver cancer. The genetic variants investigated in this study are likely to predispose to liver cancer and could affect its progression and aggressiveness. We recommend future research prioritizing the validation of these variations in clinical settings.

Keywords

References

  1. McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of hepatocellular carcinoma. Hepatology 2021;73 Suppl 1:4-13. https://doi.org/10.1002/hep.31288
  2. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. https://doi.org/10.3322/caac.21492
  3. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021;71:209-249. https://doi.org/10.3322/caac.21660
  4. Hari Kanker Sedunia 2019. Jakarta Selatan: Kementerian Kesehatan Republik Indonesia, 2019. Accessed 2023 May 21. Available from: https://www.kemkes.go.id/article/view/19020100003/harikanker-sedunia-2019.html.
  5. Villanueva A. Hepatocellular carcinoma. N Engl J Med 2019; 380:1450-1462. https://doi.org/10.1056/NEJMra1713263
  6. Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol 2013;47 Suppl:S2-S6. https://doi.org/10.1097/MCG.0b013e3182872f29
  7. Waller LP, Deshpande V, Pyrsopoulos N. Hepatocellular carcinoma: a comprehensive review. World J Hepatol 2015;7:2648-2663. https://doi.org/10.4254/wjh.v7.i26.2648
  8. Wang J, Conti DV, Bogumil D, Sheng X, Noureddin M, Wilkens LR, et al. Association of genetic risk score with NAFLD in an ethnically diverse cohort. Hepatol Commun 2021;5:1689-1703. https://doi.org/10.1002/hep4.1751
  9. Ma'ruf M, Fadli JC, Mahendra MR, Irham LM, Sulistyani N, Adikusuma W, et al. A bioinformatic approach to identify pathogenic variants for Stevens-Johnson syndrome. Genomics Inform 2023;21:e26.
  10. Puspitaningrum AN, Perwitasari DA, Adikusuma W, Djalilah GN, Dania H, Maliza R, et al. Integration of genomic databases and bioinformatic approach to identify genomic variants for Sjogren's syndrome on multiple continents. J Pharm Sci 2022; 19:71-81. https://doi.org/10.12928/mf.v19i2.23706
  11. Chen Z, Boehnke M, Wen X, Mukherjee B. Revisiting the genome-wide significance threshold for common variant GWAS. G3 (Bethesda) 2021;11:jkaa056.
  12. Li Q, Cao M, Lei L, Yang F, Li H, Yan X, et al. Burden of liver cancer: From epidemiology to prevention. Chin J Cancer Res 2022; 34:554-566. https://doi.org/10.21147/j.issn.1000-9604.2022.06.02
  13. Wege H, Schulze K, von Felden J, Calderaro J, Reig M; Rare Liver Tumors Working Group of the European Reference Network on Hepatological Diseases (ERN RARE-LIVER). Rare variants of primary liver cancer: fibrolamellar, combined, and sarcomatoid hepatocellular carcinomas. Eur J Med Genet 2021;64:104313.
  14. GTEx Portal database. Cambridge, MA: Broad Institute of MIT and Harvard, 2023. Accessed 2023 Feb 16. Available from: http://www.gtexportal.org/home/.
  15. Fitrianti F, Shatri H, Faisal E, Putranto R, Agung RA, Nainggolan L, Kalista KF, et al. Pain management in advanced hepatocellular carcinoma: a case study. J Penyakit Dalam Indones 2022;9:6.
  16. Nessa ML, Yusuf F, Mudatsir M. Relationship of Child Pugh score and quality of life of liver cirrhosis at Internal Medicine RSUDZA Banda Aceh. J Ilmiah Mahasiswa Kedokteran Biomed 2017;2:24-34.
  17. Poggiali E, Vercelli A. Sun, alcohol, and skin lesions. Emerg Care J 2023;19:11294.
  18. Li Q, Cao M, Lei L, Yang F, Li H, Yan X, et al. Burden of liver cancer: from epidemiology to prevention. Chin J Cancer Res 2022; 34:554-566. https://doi.org/10.21147/j.issn.1000-9604.2022.06.02
  19. Huang L, Sun H, Sun L, Shi K, Chen Y, Ren X, et al. Rapid, label-free histopathological diagnosis of liver cancer based on Raman spectroscopy and deep learning. Nat Commun 2023;14:48.
  20. Irham LM, Chou WH, Calkins MJ, Adikusuma W, Hsieh SL, Chang WC. Genetic variants that influence SARS-CoV-2 receptor TMPRSS2 expression among population cohorts from multiple continents. Biochem Biophys Res Commun 2020;529:263-269. https://doi.org/10.1016/j.bbrc.2020.05.179
  21. Afief AR, Irham LM, Adikusuma W, Perwitasari DA, Brahmadhi A, Chong R. Integration of genomic variants and bioinformatic-based approach to drive drug repurposing for multiple sclerosis. Biochem Biophys Rep 2022;32:101337.