Potentially Functional Genetic Variants in the NRF2 Signaling Pathway Genes are Associated With HBV-related Hepatocellular Carcinoma Survival

Gong, Rongbin; Qiu, Moqin; Cao, Ji; Zhou, Zihan; Wei, Yuying; Wen, Qiuping; Lin, Qiuling; Wei, Xiaoxia; Liang, Xiumei; Jiang, Yanji; Chen, Peiqin; Wei, Junjie; Zhan, Shicheng; Liu, Yingchun; Yu, Hongping

doi:10.7150/jca.88561



International Journal of Biological Sciences

International Journal of Medical Sciences

Theranostics

Journal of Genomics

Nanotheranostics

Global reach, higher impact

Full Text | PDF

J Cancer 2023; 14(18):3387-3396. doi:10.7150/jca.88561 This issue Cite

Research Paper

Potentially Functional Genetic Variants in the NRF2 Signaling Pathway Genes are Associated With HBV-related Hepatocellular Carcinoma Survival

Rongbin Gong^1,2,#, Moqin Qiu^3,#, Ji Cao⁴, Zihan Zhou⁴, Yuying Wei¹, Qiuping Wen¹, Qiuling Lin⁵, Xiaoxia Wei⁵, Xiumei Liang⁶, Yanji Jiang⁷, Peiqin Chen¹, Junjie Wei², Shicheng Zhan², Yingchun Liu^1,8,✉, Hongping Yu^1,8,9,✉

1. Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning 530000, China.
2. Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning 530000, China.
3. Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning 530000, China.
4. Department of Cancer Prevention and Control, Guangxi Medical University Cancer Hospital, Nanning 530000, China.
5. Department of Clinical Research, Guangxi Medical University Cancer Hospital, Nanning 530000, China.
6. Department of Disease Process Management, Guangxi Medical University Cancer Hospital, Nanning 530000, China.
7. Department of Scientific Research Dept, Guangxi Medical University Cancer Hospital, Nanning 530000, China.
8. Key Cultivated Laboratory of Cancer Molecular Medicine of Guangxi Health Commission, Guangxi Medical University Cancer Hospital, Nanning 530000, China.
9. Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning 530000, China.
^# These authors contributed equally to this work

Citation:

Gong R, Qiu M, Cao J, Zhou Z, Wei Y, Wen Q, Lin Q, Wei X, Liang X, Jiang Y, Chen P, Wei J, Zhan S, Liu Y, Yu H. Potentially Functional Genetic Variants in the NRF2 Signaling Pathway Genes are Associated With HBV-related Hepatocellular Carcinoma Survival. J Cancer 2023; 14(18):3387-3396. doi:10.7150/jca.88561. https://www.jcancer.org/v14p3387.htm

Other styles

Abstract

The nuclear factor E2-related factor 2 (NRF2) signaling pathway is one of the most important cell defense pathways. However, it is unclear whether genetic variants in NRF2 signaling pathway genes are associated with the survival of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In the present study, we utilized a new hypothesis-driven approach based on biological pathways to investigate the associations between 17919 single nucleotide polymorphisms (SNPs) in 137 NRF2 signaling pathway genes and the overall survival (OS) of 866 patients with HBV-related HCC. As a result, two independent SNPs with potential biological function were identified to be significantly associated with HBV-related HCC OS: [SLC2A9 rs28643326 T>C: hazard ratio (HR) = 0.74, 95% confidence interval (95% CI) = 0.62-0.89, P < 0.001 and SLC5A10 rs2472711 G>T: HR = 0.81, 95% CI = 0.71-0.93, P = 0.003, respectively]. The expression quantitative trait loci (eQTL) analysis further revealed that the rs28643326 C allele was significantly associated with increased levels of SLC2A9 mRNA expression (P < 0.001), and higher mRNA expression levels of SLC2A9 in adjacent normal liver tissues were associated with better survival. Although the association between the rs2472711 T allele and the mRNA expression of SLC5A10 was not statistically significant (P = 0.200), the fact that rs2472711 is located at the DNase I hypersensitivity site and is a marker for promoter and enhancer histones also suggests that it may have the function of regulating its corresponding gene expression. In conclusion, genetic variants of NRF2 signaling pathway genes may serve as potential prognostic biomarkers for HBV-related HCC and also provide a solid basis for further mechanistic exploration.

Keywords: NRF2, HBV-related HCC, SNPs, OS, eQTL

Citation styles

APA

Gong, R., Qiu, M., Cao, J., Zhou, Z., Wei, Y., Wen, Q., Lin, Q., Wei, X., Liang, X., Jiang, Y., Chen, P., Wei, J., Zhan, S., Liu, Y., Yu, H. (2023). Potentially Functional Genetic Variants in the NRF2 Signaling Pathway Genes are Associated With HBV-related Hepatocellular Carcinoma Survival. Journal of Cancer, 14(18), 3387-3396. https://doi.org/10.7150/jca.88561.

ACS

Gong, R.; Qiu, M.; Cao, J.; Zhou, Z.; Wei, Y.; Wen, Q.; Lin, Q.; Wei, X.; Liang, X.; Jiang, Y.; Chen, P.; Wei, J.; Zhan, S.; Liu, Y.; Yu, H. Potentially Functional Genetic Variants in the NRF2 Signaling Pathway Genes are Associated With HBV-related Hepatocellular Carcinoma Survival. J. Cancer 2023, 14 (18), 3387-3396. DOI: 10.7150/jca.88561.

NLM

CSE

Gong R, Qiu M, Cao J, Zhou Z, Wei Y, Wen Q, Lin Q, Wei X, Liang X, Jiang Y, Chen P, Wei J, Zhan S, Liu Y, Yu H. 2023. Potentially Functional Genetic Variants in the NRF2 Signaling Pathway Genes are Associated With HBV-related Hepatocellular Carcinoma Survival. J Cancer. 14(18):3387-3396.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.