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lncRNA HOTAIR的基因变异与中国女性上皮性卵巢癌风险

Genetic variants of lncRNA HOTAIR and risk of epithelial ovarian cancer among Chinese women.

作者信息

Wu Haijing, Shang Xiaofei, Shi Yu, Yang Zhirong, Zhao Jun, Yang Min, Li Yan, Xu Shiqiang

机构信息

Department of Gynecologic Oncology, Sichuan Cancer Hospital, Chengdu, Sichuan, China.

The First Affiliated Hospital, Nanchang University, Nanchang, China.

出版信息

Oncotarget. 2016 Jul 5;7(27):41047-41052. doi: 10.18632/oncotarget.8535.

Abstract

Ovarian cancer is one of the common female malignant tumors globally. However, exactly mechanism of ovarian cancer remained unknown. HOTAIR, a lncRNA in the mammalian HOXC locus, has been fully explored for its genetic variants, expression level and carcinogenesis, development and progression of multiple cancers, except for ovarian cancer. In this study, we hypothesized that abnormal expression of HOTAIR and common variants of HOTAIR are associated with risk of Epithelial ovarian cancer (EOC). We first evaluated the HOTAIR levels in 100 paired tissues of EOC patients and corresponding normal tissues. Results showed that the expression level of HOTAIR in EOC tissues was significantly higher than that in corresponding normal tissues. Then the genotyping analyses of HOTAIR gene was conducted in a Chinese population. The results indicated that rs4759314 and rs7958904 were significantly associated with EOC susceptibility. For rs4759314, the difference between the G allele (as the reference) and the A allele was statistically significant (adjusted OR, 1.34; 95% CI: 1.08-1.65; P = 6.8 × 10-3). For rs7958904, C allele was associated a significantly decreased EOC risk when compared with G allele (OR: 0.77; 95% CI: 0.67-0.89; P = 4.2 × 10-4). The study identified that HOTAIR variants could be a useful biomarker for the predisposition to EOC and for the early diagnosis of the disease.

摘要

卵巢癌是全球常见的女性恶性肿瘤之一。然而,卵巢癌的确切发病机制仍不清楚。HOTAIR是哺乳动物HOXC基因座中的一种长链非编码RNA(lncRNA),除卵巢癌外,其基因变异、表达水平以及在多种癌症发生、发展和进展中的作用已得到充分研究。在本研究中,我们假设HOTAIR的异常表达和常见变异与上皮性卵巢癌(EOC)的发病风险相关。我们首先评估了100例EOC患者配对组织及其相应正常组织中的HOTAIR水平。结果显示,EOC组织中HOTAIR的表达水平显著高于相应的正常组织。然后,我们在中国人群中对HOTAIR基因进行了基因分型分析。结果表明,rs4759314和rs7958904与EOC易感性显著相关。对于rs4759314,以G等位基因为参照,G等位基因与A等位基因之间的差异具有统计学意义(校正比值比[OR]为1.34;95%置信区间[CI]:1.08 - 1.65;P = 6.8×10⁻³)。对于rs7958904,与G等位基因相比,C等位基因与EOC风险显著降低相关(OR:0.77;95% CI:0.67 - 0.89;P = 4.2×10⁻⁴)。该研究表明,HOTAIR变异可能是EOC易感性和疾病早期诊断的有用生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0faa/5173041/29505641ff92/oncotarget-07-41047-g001.jpg

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