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A GALNT14 rs9679162 genotype-guided therapeutic strategy for advanced hepatocellular carcinoma: systemic or hepatic arterial infusion chemotherapy

The Pharmacogenomics Journal volume 20, pages 57–68 (2020)Cite this article

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Abstract

Although targeted agents are recommended as the first-line treatments for advanced hepatocellular carcinoma (aHCC), systemic chemotherapy or hepatic arterial infusion chemotherapy (HAIC) are still being used in Asian countries. Beside economic considerations, it was found that targeted drugs could not significantly prolong overall survival in aHCC patients with distant metastasis. In addition, chemotherapy could achieve complete response in a small proportion of patients. Here, we aimed to investigate whether combination of three previously identified single nucleotide polymorphism (SNP) predictors (GALNT14-rs9679162, WWOX-rs13338697, and rs6025211) could guide our choice between systemic chemotherapy, HAIC, and targeted agents in aHCC patients. A cohort of 237 real-world aHCC patients (171 receiving systemic chemotherapy followed by various anticancer treatments including sorafenib; 66 receiving HAIC) were included for outcome analysis. By combining the three SNP markers with or without addition of two clinical criteria (tumor diameter <8 cm, neutrophils <80%), small groups of patients were found to harbor high complete response rates to systemic chemotherapy (35.3% if the 3-SNP signature alone matched; 60.0% if clinical criteria also matched). Subsequent sorafenib treatment for chemotherapy non-responders was associated with longer overall survival (P < 0.001). In HAIC-treated patients, GALNT14-rs9679162 genotype “GG” was associated with longer overall survival (P = 0.019, median survival > 10.5 months). In conclusion, pre-test for the 3-SNP signature in aHCC patients could identify potential systemic chemotherapy or HAIC responders. Chemotherapy non-responders still benefited from subsequent sorafenib treatment. Accordingly, we propose a roadmap for aHCC patients when chemotherapy or HAIC is to be used.

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Acknowledgements

The authors thank technicians in Liver Research Center, Chang Gung Memorial Hospital for their excellent technical help.

Funding

This study was supported by grants from Chang Gung Memorial Hospital, Linkou branch (CMRPG3F1602) and from Ministry of Health and Welfare (MOHW107-TDU-B-212-114023).

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Authors and Affiliations

  1. Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan

    Chen-Chun Lin, Chao-Wei Hsu, Yi-Cheng Chen, Ming-Ling Chang, Ming-Wei Lai, Rong-Nan Chien & Chau-Ting Yeh

  2. Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan

    Kung-Hao Liang

  3. Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

    Chih-Lang Lin

  4. Department of Biochemistry, School of Medicine, Chang Gung University, Taoyuan, Taiwan

    Kwang-Huei Lin

  5. Molecular Medicine Research Laboratory, Chang Gung University, Taoyuan, Taiwan

    Chau-Ting Yeh

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  1. Chen-Chun Lin
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Contributions

C.T.Y. designed and supervised the study; C.T.Y. and C.C.L. drafted the paper; C.C.L., C.W.H., Y.C.C., M.L.C., M.W.L., C.L.L., and R.N.C. collected samples, performed all assays, and interpreted the data; C.T.Y. and K.H.L. performed statistical analysis.

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Correspondence to Chau-Ting Yeh.

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Lin, CC., Hsu, CW., Chen, YC. et al. A GALNT14 rs9679162 genotype-guided therapeutic strategy for advanced hepatocellular carcinoma: systemic or hepatic arterial infusion chemotherapy. Pharmacogenomics J 20, 57–68 (2020). https://doi.org/10.1038/s41397-019-0106-0

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