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GRP78 3'UTR 中的变异与可切除肝细胞癌的总生存率无关。

The 3' UTR variants in the GRP78 are not associated with overall survival in resectable hepatocellular carcinoma.

机构信息

Cancer Institute and Affiliated Tumor Hospital, Guangzhou Medical College, Guangzhou, China.

出版信息

PLoS One. 2011 Mar 22;6(3):e17783. doi: 10.1371/journal.pone.0017783.

DOI:10.1371/journal.pone.0017783
PMID:21445355
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3062561/
Abstract

BACKGROUND

Elevated glucose-regulated protein 78 (GRP78) levels in tissues have been known to be related with poor prognosis in hepatocellular carcinoma (HCC) patients. Though the variants in the 3' untranslated region (UTR) of GRP78 gene were not associated with HCC risk, we wonder whether these polymorphisms affect survival of HCC patients.

METHODOLOGY/PRINCIPAL FINDINGS: Blood samples of HCC patients were maintained in our specimen bank between 1996 to 2003. DNA from 576 unrelated and resectable patients with HCC was typed for rs16927997 (T>C), rs1140763 (T>C) and rs12009 (T>C) by TaqMan assays. The Kaplan-Meier method and log-rank test were used to estimate overall survival. Linkage disequilibrium (LD) analysis identified a total of 3 haplotypes and 6 diplotypes in this region. The distribution of haplotype was not related to the clinical characteristics. Univariate analysis showed that the allele, genotype, haplotype and diplotype did not effect the survival. None of the clinical features show a significant association (P(corrected)>0.05) with overall patient outcome in multiple comparisons.

CONCLUSIONS/SIGNIFICANCE: There is no noteworthy influence of 3' UTR variants in the GRP78 on prognosis of resectable HCC in the Chinese population.

摘要

背景

已知组织中葡萄糖调节蛋白 78(GRP78)水平升高与肝细胞癌(HCC)患者的预后不良有关。尽管 GRP78 基因 3'非翻译区(UTR)的变异与 HCC 风险无关,但我们想知道这些多态性是否会影响 HCC 患者的生存。

方法/主要发现:我们的标本库中保存了 1996 年至 2003 年间的 HCC 患者的血液样本。通过 TaqMan 分析对 576 名无关联且可切除的 HCC 患者的 DNA 进行 rs16927997(T>C)、rs1140763(T>C)和 rs12009(T>C)分型。采用 Kaplan-Meier 方法和对数秩检验估计总生存率。连锁不平衡(LD)分析确定了该区域的总共 3 种单倍型和 6 种二倍型。单倍型的分布与临床特征无关。单因素分析显示,等位基因、基因型、单倍型和二倍型对生存没有影响。在多次比较中,没有任何临床特征与总体患者结局有显著关联(P(校正)>0.05)。

结论/意义:在中国人群中,GRP78 的 3'UTR 变异对可切除 HCC 的预后没有显著影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b7b/3062561/d8ea5ef649c6/pone.0017783.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b7b/3062561/d8ea5ef649c6/pone.0017783.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b7b/3062561/d8ea5ef649c6/pone.0017783.g001.jpg

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Hepatology. 2010 Dec;52(6):2034-43. doi: 10.1002/hep.23943.
3
Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers.
内质网应激相关基因 GRP78 的内含子变异可提高对持续 HBV 感染者肝硬化的预测能力。
PLoS One. 2011;6(7):e21997. doi: 10.1371/journal.pone.0021997. Epub 2011 Jul 14.
全基因组关联研究鉴定出 1p36.22 是慢性乙型肝炎病毒携带者肝细胞癌的一个新易感位点。
Nat Genet. 2010 Sep;42(9):755-8. doi: 10.1038/ng.638. Epub 2010 Aug 1.
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