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Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients

BACKGROUND: The NF-κB signaling pathway plays an important role in associating inflammation with tumor development and progression. However, few studies have reported that roles of genetic variants of the NF-κB signaling pathway genes in survival of patients with HBV-related hepatocellular carcinoma...

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Autores principales: Huang, Qiongguang, Liu, Yingchun, Qiu, Moqin, Lin, Qiuling, Wei, Xueyan, Zhou, Zihan, Liang, Xiumei, Li, Runwei, Chen, Weiyi, Zhou, Xianguo, Yu, Hongping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478184/
https://www.ncbi.nlm.nih.gov/pubmed/36119471
http://dx.doi.org/10.3389/fonc.2022.990160
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author Huang, Qiongguang
Liu, Yingchun
Qiu, Moqin
Lin, Qiuling
Wei, Xueyan
Zhou, Zihan
Liang, Xiumei
Li, Runwei
Chen, Weiyi
Zhou, Xianguo
Yu, Hongping
author_facet Huang, Qiongguang
Liu, Yingchun
Qiu, Moqin
Lin, Qiuling
Wei, Xueyan
Zhou, Zihan
Liang, Xiumei
Li, Runwei
Chen, Weiyi
Zhou, Xianguo
Yu, Hongping
author_sort Huang, Qiongguang
collection PubMed
description BACKGROUND: The NF-κB signaling pathway plays an important role in associating inflammation with tumor development and progression. However, few studies have reported that roles of genetic variants of the NF-κB signaling pathway genes in survival of patients with HBV-related hepatocellular carcinoma (HBV-HCC), especially with regards to potentially functional SNPs. METHODS: We used multivariate Cox proportional hazards regression to evaluate associations between 2,060 single nucleotide polymorphisms (SNPs) in 20 NF-κB signaling pathway genes and survival of 866 HBV-HCC patients, which were randomly split (1:1) into discovery and validation datasets. Expression quantitative trait loci (eQTL) analysis was conducted to identify associations between survival-associated SNPs and mRNA expression of corresponding genes. Furthermore, online database was used to assess mRNA expression of corresponding genes and survival. Finally, receiver operating characteristic (ROC) curves were used to assess the prediction accuracy of models integrating both clinical and genetic variables on HCC survival. RESULTS: A total of 6 SNPs in MAP3K14 remained significantly associated with OS of HBV-HCC patients (P<0.05, BFDP<0.8). Further eQTL analysis demonstrated that significant correlations between the rs2074292 (G>A) A allele was associated with higher mRNA expression levels of MAP3K14 (P=0.044) in normal liver tissue, which was associated with worse survival of HBV-HCC patients. In the additive model, after adjusting for age, sex, smoking status, drinking status, AFP level, cirrhosis, embolus and BCLC stage, the combined dataset showed that HBV-HCC patients carrying the rs2074292 AA and GA genotypes (HR=1.71, 95%CI= 1.29-2.27, P=0.000) (HR=1.40, 95%CI=1.10-1.77, P=0.005) have worse OS than GG genotype, respectively. The addition of risk genotypes to the prediction models increased the AUC significantly from 71.15% to 73.11% (P=0.012) and from 72.55% to 74.21% (P=0.010) for 1-year and 3-year OS, respectively. CONCLUSION: Our study indicated that MAP3K14 rs2074292 A allele may be a potential predictor of HBV-HCC survival, likely regulating MAP3K14 mRNA expression.
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spelling pubmed-94781842022-09-17 Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients Huang, Qiongguang Liu, Yingchun Qiu, Moqin Lin, Qiuling Wei, Xueyan Zhou, Zihan Liang, Xiumei Li, Runwei Chen, Weiyi Zhou, Xianguo Yu, Hongping Front Oncol Oncology BACKGROUND: The NF-κB signaling pathway plays an important role in associating inflammation with tumor development and progression. However, few studies have reported that roles of genetic variants of the NF-κB signaling pathway genes in survival of patients with HBV-related hepatocellular carcinoma (HBV-HCC), especially with regards to potentially functional SNPs. METHODS: We used multivariate Cox proportional hazards regression to evaluate associations between 2,060 single nucleotide polymorphisms (SNPs) in 20 NF-κB signaling pathway genes and survival of 866 HBV-HCC patients, which were randomly split (1:1) into discovery and validation datasets. Expression quantitative trait loci (eQTL) analysis was conducted to identify associations between survival-associated SNPs and mRNA expression of corresponding genes. Furthermore, online database was used to assess mRNA expression of corresponding genes and survival. Finally, receiver operating characteristic (ROC) curves were used to assess the prediction accuracy of models integrating both clinical and genetic variables on HCC survival. RESULTS: A total of 6 SNPs in MAP3K14 remained significantly associated with OS of HBV-HCC patients (P<0.05, BFDP<0.8). Further eQTL analysis demonstrated that significant correlations between the rs2074292 (G>A) A allele was associated with higher mRNA expression levels of MAP3K14 (P=0.044) in normal liver tissue, which was associated with worse survival of HBV-HCC patients. In the additive model, after adjusting for age, sex, smoking status, drinking status, AFP level, cirrhosis, embolus and BCLC stage, the combined dataset showed that HBV-HCC patients carrying the rs2074292 AA and GA genotypes (HR=1.71, 95%CI= 1.29-2.27, P=0.000) (HR=1.40, 95%CI=1.10-1.77, P=0.005) have worse OS than GG genotype, respectively. The addition of risk genotypes to the prediction models increased the AUC significantly from 71.15% to 73.11% (P=0.012) and from 72.55% to 74.21% (P=0.010) for 1-year and 3-year OS, respectively. CONCLUSION: Our study indicated that MAP3K14 rs2074292 A allele may be a potential predictor of HBV-HCC survival, likely regulating MAP3K14 mRNA expression. Frontiers Media S.A. 2022-09-02 /pmc/articles/PMC9478184/ /pubmed/36119471 http://dx.doi.org/10.3389/fonc.2022.990160 Text en Copyright © 2022 Huang, Liu, Qiu, Lin, Wei, Zhou, Liang, Li, Chen, Zhou and Yu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Huang, Qiongguang
Liu, Yingchun
Qiu, Moqin
Lin, Qiuling
Wei, Xueyan
Zhou, Zihan
Liang, Xiumei
Li, Runwei
Chen, Weiyi
Zhou, Xianguo
Yu, Hongping
Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients
title Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients
title_full Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients
title_fullStr Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients
title_full_unstemmed Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients
title_short Potentially functional variants of MAP3K14 in the NF-κB signaling pathway genes predict survival of HBV-related hepatocellular carcinoma patients
title_sort potentially functional variants of map3k14 in the nf-κb signaling pathway genes predict survival of hbv-related hepatocellular carcinoma patients
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9478184/
https://www.ncbi.nlm.nih.gov/pubmed/36119471
http://dx.doi.org/10.3389/fonc.2022.990160
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