The Impact of GPC3 rs2267531 Polymorphism on Hepatocellular Carcinoma Susceptibility

Authors

DOI:

https://doi.org/10.24079/CAJMS.2025.01.001

Keywords:

HCC, liver cancer, SNP, genotype, hepatitis virus (B,C,D)

Abstract

Objectives: To evaluate the association between the GPC3 rs2267531 polymorphism and hepatocellular carcinoma (HCC) in individuals from Mongolia. Methods: This study included 270 participants, consisting of 110 males and 160 females, with a mean age of 61.0 years (±9.5). Serum samples were collected from all participants, who were categorized into three groups: 90 patients with hepatocellular carcinoma (HCC), 90 individuals in the risk group (RG), and 90 healthy controls. The collected samples were analyzed using allele-specific polymerase chain reaction (PCR). Results: No significant differences in genotype and allele frequencies were observed between the HCC group and the risk or control groups. However, the frequency of the GPC3 C allele was significantly higher in females in the HCC group. Additionally, the protective GG genotype of GPC3 was found to have a significantly lower frequency in females in the HCC group. In contrast, HCV-positive individuals exhibited a higher frequency of the GC genotype. Conclusion: The GPC3 C allele frequency is associated with HCC in females, while the heterozygote GC genotype is linked to HCV infection in both genders. These findings suggest that the GPC3 rs2267531 polymorphism may play a role in HCC susceptibility, particularly in relation to gender and HCV status.

Downloads

Download data is not yet available.
Abstract
75

Author Biography

Batchimeg Batbaatar, Department of Molecular Biology and Genetics, School of Bio Medicine, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia;

Institute of Medical Sciences, Ulaanbaatar, Mongolia;

References

1 Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11(4):317-370. https://doi.org/10.1007/s12072-017-9799-9

2. Trad D, Bibani N, Sabbah M, et al. Known, new and emerging risk factors of hepatocellular carcinoma (review). Presse Med. 2017;46(11):1000-1007. https://doi.org/10.1016/j.lpm.2017.09.025

3. Baatarkhuu O, Malov S, Rasulov R, et al. Hepatocellular carcinoma associated with hepatitis B and C in mongoloids and caucasians of North-East Asia. Infectious diseases: News, Opinions, Training. 2021;10:38-44. https://doi.org/10.33029/2305-3496-2021-10-4-38-44

4. Baatarkhuu O, Gerelchimeg T, Munkh-Orshikh D, Batsukh B, Sarangua G, Amarsanaa J. Epidemiology, Genotype Distribution, Prognosis, Control, and Management of Viral Hepatitis B, C, D, and Hepatocellular Carcinoma in Mongolia. Euroasian J Hepatogastroenterol. 2018;8(1):57-62. https://doi.org/10.5005/jp-journals-10018-1260

5. Dashtseren B, Genden Z, Oidovsambuu O, et al. Treatment of Chronic HCV Infection with Direct Acting Antivirals. Centr Asia J Med Sci. 2021;7(3):222-230. https://doi.org/10.24079/cajms.2021.09.007

6. Massarweh NN, El-Serag HB. Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

Cancer Control. 2017;24(3):1073274817729245. https://doi.org/10.1177/1073274817729245

7. Data Visualization Tools for Exploring the Global Cancer

Burden in 2020. https://gco.iarc.fr/today/en.

8. Llovet JM, Zucman-Rossi J, Pikarsky E, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2016;2:16018. https://doi.org/10.1038/nrdp.2016.18

9. Kulik L, El-Serag HB. Epidemiology and Management of Hepatocellular Carcinoma. Gastroenterol 2019;156(2):477-491.e471. https://doi.org/10.1053/j.gastro.2018.08.065

10. Wu EM, Wong LL, Hernandez BY, et al. Gender differences in hepatocellular cancer: disparities in nonalcoholic fatty liver disease/steatohepatitis and liver transplantation.

Hepatoma Res. 2018;4. https://doi.org/10.20517/2394-5079.2018.87

11. Center for Health Development. Health indicators. 2020. https://hdc.gov.mn/media/uploads/2022-05/health_indicator_2020_ENG.pdf

12. Tunissiolli NM, Castanhole-Nunes MMU, Biselli-Chicote PM, et al. Hepatocellular Carcinoma: a Comprehensive Review of Biomarkers, Clinical Aspects, and Therapy. Asian Pac J

Cancer Prev. 2017;18(4):863-872.

13. Khan S, Blackburn M, Mao DL, et al. Glypican-3 (GPC3) expression in human placenta: localization to the differentiated syncytiotrophoblast. Histol histopathol. 2001;16(1):71-78. https://doi.org/10.1203/00006450-199904020-00327

14. Capurro M, Martin T, Shi W, et al. Glypican-3 binds to Frizzled and plays a direct role in the stimulation of canonical Wnt signaling. J cell sci. 2014;127(Pt 7):1565-1575. https://doi.org/10.1242/jcs.140871

15. Liu H, Li P, Zhai Y, et al. Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma. World J Gastroenterol. 2010;16(35):4410-4415. https://doi.org/10.3748/wjg.v16.i35.4410

16. Capurro M, Wanless IR, Sherman M, et al. Glypican-3: a novel serum and histochemical marker for hepatocellular carcinoma. Gastroenterol. 2003;125(1):89-97. https://doi.org/10.1016/s0016-5085(03)00689-9

17. Motawi TMK, Sadik NAH, Sabry D, et al. rs2267531, a promoter SNP within glypican-3 gene in the X chromosome, is associated with hepatocellular carcinoma in Egyptians. Scientific Reports. 2019;9(1):6868. https://doi.org/10.1038/s41598-019-43376-3

18. Batsaikhan O, Chimed-Ochir O, Kubo T, et al. The burden of liver cancer in Mongolia from 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Front Oncol. 2024;14:1381173. https://doi.org/10.3389/fonc.2024.1381173

19. Ali M, Liu X, Pillai EN, et al. Characterizing the genetic differences between two distinct migrant groups from Indo-European and Dravidian speaking populations in India. BMC Genet. 2014;15:86. https://doi.org/10.1186/1471-2156-15-86

20. Su H, Wang M, Li X, et al. Population genetic admixture and evolutionary history in the Shandong Peninsula inferred from integrative modern and ancient genomic resources. BMC Genomics. 2024;25(1):611. https://doi.org/10.1186/s12864-024-10514-9

21. Wang Z, Sun L. Major sex differences in allele frequencies for X chromosomal variants in both the 1000 Genomes Project and gnomAD. Plos Genet. 2022;18(5):e1010231. https://doi.org/10.1371/journal.pgen.1010231

22. Schurz H, Salie M, Tromp G, et al. The X chromosome and sex-specific effects in infectious disease susceptibility. Hum Genomics. 2019;13(1):2. https://doi.org/10.1186/s40246-018-0185-z

23. Talebizadeh Z, Simon SD, Butler MG. X chromosome gene expression in human tissues: male and female comparisons. Genomics. 2006;88(6):675-681. https://doi.org/10.1016/j.ygeno.2006.07.016

24. Midorikawa Y, Ishikawa S, Iwanari H, et al. Glypican-3, overexpressed in hepatocellular carcinoma, modulates FGF2 and BMP-7 signaling. Int J Cancer. 2003;103(4):455-465. https://doi.org/10.1002/ijc.10856

25. Zhu ZW, Friess H, Wang L, et al. Enhanced glypican-3 expression differentiates the majority of hepatocellular carcinomas from benign hepatic disorders. Gut. 2001;48(4):558-564. https://doi.org/10.1136/gut.48.4.558

26. Lin Q, Xiong LW, Pan XF, et al. Expression of GPC3 protein and its significance in lung squamous cell carcinoma. Med Oncol. 2012;29(2):663-669. https://doi.org/10.1007/s12032-011-9973-1

27. Ushiku T, Uozaki H, Shinozaki A, et al. Glypican 3-expressing gastric carcinoma: distinct subgroup unifying hepatoid, clear-cell, and alpha-fetoprotein-producing gastric carcinomas. Cancer Sci. 2009;100(4):626-632. https://doi.org/10.1111/j.1349-7006.2009.01108.x

28. Maeda D, Ota S, Takazawa Y, et al. Glypican-3 expression in clear cell adenocarcinoma of the ovary. Mod Pathol. 2009;22(6):824-832. https://doi.org/10.1038/modpathol.2009.40

29. Ortiz MV, Roberts SS, Glade Bender J, et al. Immunotherapeutic Targeting of GPC3 in Pediatric Solid Embryonal Tumors. Front Oncol. 2019;9:108. https://doi.org/10.3389/fonc.2019.00108

30. Paine-Saunders S, Viviano BL, Zupicich J, et al. glypican-3 controls cellular responses to Bmp4 in limb patterning and skeletal development. Dev Biol. 2000;225(1):179-187. https://doi.org/10.1006/dbio.2000.9831

31. Iglesias BV, Centeno G, Pascuccelli H, et al. Expression pattern of glypican-3 (GPC3) during human embryonic and fetal development. Histol Histopathol. 2008;23(11):1333-1340.

Published

2025-03-31

How to Cite

Batbaatar, B., Enkhbat, Y., Tuvshiunsaikhan, O., Dashzeveg, Y., Bat-Erdene, M., Unurbuyan, K., … Jav, S. (2025). The Impact of GPC3 rs2267531 Polymorphism on Hepatocellular Carcinoma Susceptibility. Central Asian Journal of Medical Sciences, 11(1), 1–10. https://doi.org/10.24079/CAJMS.2025.01.001

Issue

Section

Articles