A genetic variant in the promoter region of miR-106b-25 cluster predict clinical outcome of HBV-related hepatocellular carcinoma in Chinese

Fuzhen Qi; Mingde Huang; Yun Pan; Yao Liu; Jibin Liu; Juan Wen; Kaipeng Xie; Hongbing Shen; Hongxia Ma; Yi Miao; Zhibin Hu

doi:10.1371/journal.pone.0085394

A genetic variant in the promoter region of miR-106b-25 cluster predict clinical outcome of HBV-related hepatocellular carcinoma in Chinese

PLoS One. 2014 Jan 8;9(1):e85394. doi: 10.1371/journal.pone.0085394. eCollection 2014.

Authors

Fuzhen Qi¹, Mingde Huang², Yun Pan³, Yao Liu³, Jibin Liu⁴, Juan Wen³, Kaipeng Xie³, Hongbing Shen⁵, Hongxia Ma⁵, Yi Miao⁶, Zhibin Hu⁵

Affiliations

¹ Department of Hepatopancreatobiliary Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.
² Department of Medical Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.
³ Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
⁴ Department of Hepatobiliary Surgery, Nantong Tumor Hospital, Nantong, Jiangsu, China.
⁵ Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China ; State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China.
⁶ Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Abstract

Background: MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients.

Methods: The SNP, rs999885, was genotyped by using the TaqMan allelic discrimination Assay in 414 intermediate or advanced HCC patients. Log-rank test and Cox proportional hazard models were used for survival analysis.

Results: The variant genotypes of rs999885 were associated with a significantly decreased risk of death for intermediate or advanced HCC [additive model: adjusted hazard ratio (HR) = 0.76,95% confidence intervals (CI) = 0.59-0.97]. Further stepwise regression analysis suggested that rs999885 was an independently protective factor for the prognosis of HCC in the final model (additive model: adjusted HR = 0.72, 95% CI = 0.56-0.91, P = 0.007).

Conclusions: These findings indicate that the A to G base change of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Asian People
Carcinoma, Hepatocellular / ethnology
Carcinoma, Hepatocellular / etiology
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / mortality
Female
Hepatitis B / complications
Hepatitis B / ethnology
Hepatitis B / genetics*
Hepatitis B / mortality
Humans
Introns
Liver Neoplasms / ethnology
Liver Neoplasms / etiology
Liver Neoplasms / genetics*
Liver Neoplasms / mortality
Male
MicroRNAs / genetics*
Middle Aged
Minichromosome Maintenance Complex Component 7 / genetics*
Neoplasm Staging
Polymorphism, Single Nucleotide
Promoter Regions, Genetic*
Proportional Hazards Models
Survival Analysis

Substances

MIRN106 microRNA, human
MicroRNAs
MCM7 protein, human
Minichromosome Maintenance Complex Component 7

Grants and funding

This work was funded by the National Natural Science Foundation of China (81372606 and 81072344), Project supported by the National Key Basic Research Program Grant (2013CB911400), the project supported by the National Science Foundation for Distinguished Young Scholars of China (81225020), Foundation of Jiangsu Province for Distinguished Young Scholars(BK2012042), Foundation for the Program for New Century Excellent Talents in University (NCET-10-0178), the Fok Ying-Tong Education Foundation for Young Teachers in the Higher Education Institutions (122031), Young tip-top talents support program by the Organization Department of the CPC Central Committee, the Author of National Excellent Doctoral Dissertation (201081) , Jiangsu Province Clinical Science and Technology Projects (BL2012008) and the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.