Xavier-Magalhães Ana, Oliveira Ana I, de Castro Joana Vieira, Pojo Marta, Gonçalves Céline S, Lourenço Tatiana, Viana-Pereira Marta, Costa Sandra, Linhares Paulo, Vaz Rui, Nabiço Rui, Amorim Júlia, Pinto Afonso A, Reis Rui M, Costa Bruno M
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
ICVS/3B's - PT Government Associate Laboratory, University of Minho, Braga/Guimarães, Campus de Gualtar, 4710-057, Braga, Portugal.
J Neurooncol. 2017 Mar;132(1):27-34. doi: 10.1007/s11060-016-2345-0. Epub 2017 Jan 12.
Abnormal expression of the long non-coding RNA HOX transcript antisense intergenic RNA (HOTAIR) is oncogenic in several human cancers, including gliomas. The HOTAIR single nucleotide polymorphisms (SNPs) rs920778 (C > T) and rs12826786 (C > T) present in the intronic enhancer and promoter regions of HOTAIR, respectively, are associated with expression, cancer susceptibility, and patient prognosis in some tumor types. However, the relevance of these HOTAIR SNPs has not been studied in glioma. Here, we report a case-control study comprising 177 Portuguese glioma patients and 199 cancer-free controls. All subjects were genotyped by PCR and restriction fragment length polymorphism (RFLP). No statistically significant differences were found in the genotype or allele distributions of either rs920778 or rs12826786 between glioma patients and controls, suggesting these SNPs are not associated with glioma risk. No significant associations were found between rs920778 variants and HOTAIR expression levels, while rs12826786 CT genotype was associated with increased intratumoral HOTAIR RNA levels when compared to TT genotype (p-value = 0.04). Univariate (Log-rank) and multivariate (Cox proportional) analyses showed both rs920778 CT and rs12826786 CT genotypes were significantly associated with longer overall survival of WHO grade III anaplastic oligodendroglioma patients. Our results suggest that HOTAIR SNPs rs920778 and rs12826786 do not play a significant role in glioma susceptibility, but may be important prognostic factors in anaplastic oligodendroglioma patients. Future studies are warranted to validate and expand these findings, and to further dissect the importance of these SNPs in glioma.
长链非编码RNA HOX转录本反义基因间RNA（HOTAIR）的异常表达在包括神经胶质瘤在内的多种人类癌症中具有致癌性。HOTAIR的单核苷酸多态性（SNP）rs920778（C>T）和rs12826786（C>T）分别存在于HOTAIR的内含子增强子和启动子区域，在某些肿瘤类型中与表达、癌症易感性和患者预后相关。然而，这些HOTAIR SNP在神经胶质瘤中的相关性尚未得到研究。在此，我们报告一项病例对照研究，该研究包括177例葡萄牙神经胶质瘤患者和199例无癌对照。所有受试者均通过聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）进行基因分型。在神经胶质瘤患者和对照之间，rs920778或rs12826786的基因型或等位基因分布均未发现统计学上的显著差异，这表明这些SNP与神经胶质瘤风险无关。rs920778变异与HOTAIR表达水平之间未发现显著关联，而与TT基因型相比，rs12826786 CT基因型与肿瘤内HOTAIR RNA水平升高相关（p值=0.04）。单因素（对数秩）和多因素（Cox比例）分析显示，rs920778 CT和rs12826786 CT基因型均与世界卫生组织（WHO）III级间变性少突神经胶质瘤患者较长的总生存期显著相关。我们的结果表明，HOTAIR SNP rs920778和rs12826786在神经胶质瘤易感性中不发挥重要作用，但可能是间变性少突神经胶质瘤患者的重要预后因素。有必要开展进一步研究以验证和扩展这些发现，并进一步剖析这些SNP在神经胶质瘤中的重要性。
