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J Cancer 2022; 13(11):3251-3257. doi:10.7150/jca.75754 This issue Cite

Research Paper

Analysis of MUC6 Genetic Variants on the Clinicopathologic Characteristics of Patients with Hepatocellular Carcinoma

Hsiang-Lin Lee^1,2,3#, Yi-Chung Chien^4,5,6,7,8#, Hsiang-Ling Wang⁹, Chun-Hung Hua¹⁰, Liang-Chih Liu^11,12, Guo-Wei Wu⁴, Li-Yuan Bai^13✉, Shun-Fa Yang^14,15✉, Yung-Luen Yu^{4,5,6,7,8,16✉}

1. School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
2. Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
3. Department of Surgery, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
4. Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan.
5. Ph.D. Program for Translational Medicine, China Medical University, Taichung 40402, Taiwan.
6. Institute of Translational Medicine and New Drug Development, Taichung 40402, Taiwan.
7. Drug Development Center, Research Center for Cancer Biology, China Medical University, Taichung 40402, Taiwan.
8. Center for Molecular Medicine, China Medical University Hospital, Taichung 40402, Taiwan.
9. Department of Beauty Science, National Taichung University of Science and Technology, Taichung 40404, Taiwan.
10. Department of Otorhinolaryngology Head and Neck Surgery, China Medical University Hospital, Taichung, Taiwan.
11. School of Medicine, College of Medicine, China Medical University, Taichung 40402, Taiwan.
12. Department of Surgery, China Medical University Hospital, Taichung 40402, Taiwan.
13. Department of Hematology and Oncology, China Medical University Hospital, Taichung 40402, Taiwan.
14. Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
15. Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
16. Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, Taiwan.
#These authors contributed equally to this work.

✉ Corresponding authors: lybai6com (L.-Y. B.); ysfedu.tw (S.-F.Y.); ylyucmu.edu.tw (Y.-L.Y.).

Abstract

Hepatocellular carcinoma (HCC) is the leading malignancy associated with cancer-related deaths worldwide. Many studies have indicated that mucin (MUC) expression plays an important role in cancer metastasis and recurrence. MUC6 expression is observed in gastric and oncocytic phenotypes and may play an important role during cancer progression. We found the level of MUC6 is lower in HCC patients but did not affect the survival of HCC patients. Therefore, in this study, we investigated the combined effect of MUC6 polymorphisms and exposure to environmental carcinogens on the susceptibility to and clinicopathological characteristics of HCC. Three single-nucleotide polymorphisms (SNPs) of MUC6 (rs61869016, rs6597947, and rs7481521) from 1197 healthy controls and 423 HCC patients were analyzed using real-time PCR. After adjusting for other co-variants, we found that carrying a CC genotype at MUC6 rs61869016 had a lower risk of developing HCC than wildtype carriers. Moreover, patients with a smoking habit who carried the C allele of rs61869016 and T allele of rs7481521 had a higher (B or C) Child-Pugh score than other genotypes, suggesting significant functional compromise and decompensated disease. Therefore, our findings suggest that genetic variations in MUC6 may corelate to HCC and indicate progression in HCC patients.

Keywords: hepatocellular carcinoma, MUC6, Child-Pugh score, single-nucleotide polymorphisms

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