GALNT14-rs9679162 Genotypes Predict Post-immunotherapy Side Effect and Survival in Patients with Hepatitis B Virus-related Hepatocellular Carcinoma

Po-Ting Lin; Wei Teng; Wei-Ting Chen; Yu-De Chu; Chung-Wei Su; Yi-Chung Hsieh; Chen-Chun Lin; Yung-Chang Lin; Chun-Yen Lin; Chau-Ting Yeh; Shi-Ming Lin

doi:10.7150/jca.133473

GALNT14-rs9679162 Genotypes Predict Post-immunotherapy Side Effect and Survival in Patients with Hepatitis B Virus-related Hepatocellular Carcinoma

J Cancer. 2026 Jun 10;17(6):1220-1228. doi: 10.7150/jca.133473. eCollection 2026.

Authors

Po-Ting Lin^{1

2

3}, Wei Teng^{1

2}, Wei-Ting Chen^{1

2

4}, Yu-De Chu⁴, Chung-Wei Su^{1

2}, Yi-Chung Hsieh^{1

2}, Chen-Chun Lin^{2

5}, Yung-Chang Lin^{2

6}, Chun-Yen Lin^{1

2}, Chau-Ting Yeh^{1

2

4

7}, Shi-Ming Lin^{1

2}

Affiliations

¹ Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou branch, No. 5, Fuxing St., Guishan Dist., Taoyuan City, 333, Taiwan.
² College of Medicine, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 333, Taiwan.
³ Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, No.259, Wenhua 1st Rd., Guishan Dist., Taoyuan City 333, Taiwan.
⁴ Liver Research Center, Linkou Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan Dist., Taoyuan City, 333, Taiwan.
⁵ Department of Gastroenterology and Hepatology, New Taipei Municipal Tucheng Hospital, No.6, Sec.2, Jincheng Rd., Tucheng Dist., New Taipei City 236, Taiwan.
⁶ Department of Hematology-Oncology, Chang Gung Memorial Hospital, Linkou branch, No. 5, Fuxing St., Guishan Dist., Taoyuan City, 333, Taiwan.
⁷ Institute of Stem Cell and Translational Cancer Research, Linkou Chang Gung Memorial Hospital, No. 5, Fuxing St., Guishan Dist., Taoyuan City, 333, Taiwan.

Abstract

Introduction: Genomic alterations have been reported to correlate with patients' response to immune checkpoint inhibitor (ICI) therapy in hepatocellular carcinoma (HCC). The present study aimed to examine whether single nucleotide polymorphism (SNP) is associated with ICI treatment-related side effects and progression-free survival (PFS) in HCC patients.

Methods: This retrospective study included 96 patients with HBV-related HCC receiving ICI (atezolizumab plus bevazizumab) therapy between 2020 and 2023. Five SNPs derived from a previous genome-wide association study linking to chemotherapy responses in HCC patients were included. Their predictive values for PFS and side effects were examined.

Results: After ICI therapy, patients with GALNT14-rs9679162 "GG" genotype (median PFS = 19.7 months, 95% confidence interval [CI]: 12.3-35.7; p = 0.032) had a longer PFS, whereas GALNT14-rs675230, BMP7-rs6025211, WWOX-rs13338697 or WWOX-rs13333314 were not associated with PFS (all p > 0.05). GALNT14-rs9679162 "GG" genotype (odds ratio [OR] = 0.298, 95% CI: 0.096-0.926; p = 0.036) was also associated with a decreased risk of post-treatment high-grade aspartate aminotransferase (AST) elevation. Multivariate analysis showed that GALNT14-rs9679162 "GG" genotype (hazard ratio [HR] = 0.433, 95% CI: 0.212-0.886; p = 0.022) and high initial albumin-bilirubin (ALBI) grade (HR = 2.053, 95% CI: 1.153-3.590; p = 0.014) were independently associated with PFS.

Conclusions: Genetic variant of an SNP, GALNT14-rs9679162, predicts post-treatment PFS and side effect in HBV-related HCC patients receiving ICIs therapy.

Keywords: hepatocellular carcinoma (HCC); progression-free survival (PFS); rs6752303; side effects; single nucleotide polymorphism (SNP).