Zhang Xunlei, Gu Dongying, Du Mulong, Wang Meilin, Cao Chunxiang, Shen Lili, Kuang Meng, Tan Yongfei, Huo Xinying, Gong Weida, Xu Zhi, Chen Jinfei, Zhang Zhengdong, Tang Cuiju
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China.
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 211166, China.
Int J Mol Sci. 2014 Dec 10;15(12):22902-17. doi: 10.3390/ijms151222902.
The orphan nuclear receptor (NR5A2), which belongs to the NR5A subfamily of nuclear receptors, is expressed in developing and adult tissues of endodermal origin, and can contribute to the development of several cancers through regulating cell proliferation. NR5A2 (rs3790843 and rs3790844) single nucleotide polymorphisms (SNPs) genotyping were examined in DNA samples, extracted from paraffin-embedded cancer tissue. Clinicopathologic and follow-up data were collected from 944 patients with gastric cancer (GC). Associations of the 2 SNPs with the progression and prognosis in gastric cancer patients were analyzed using the SPSS version 18.0. We found that NR5A2 rs3790843 polymorphism was significantly associated with the risk of GC which had regional lymph node metastasis (p = 0.044) or distant metastasis (p = 0.020). Our results also indicated that rs3790844 polymorphism was associated with the increased overall survival (OS) of GC patients in the dominant model (GG vs. GA/AA, HR (hazard ratio) = 0.823, 95% CI (confidence interval) = 0.679-0.997), suggesting a potential protective role of the variant A allele. Additionally, in the stratified analysis, both NR5A2 rs3790843 and rs3790844 polymorphism were associated with significantly lower risk of death in the groups of female, tumor size >5 cm in a dominant model. Our results represent the first demonstration that the NR5A2 rs3790844 polymorphism is associated with increased OS of GC patients in the dominant model, and similar results were found among the female group and tumor size >5 cm group for NR5A2 rs3790843 polymorphism. Further validation in other larger studies with different ethnic populations and functional evaluations are needed.
孤儿核受体（NR5A2）属于核受体的NR5A亚家族，在发育中的内胚层起源组织和成年组织中表达，并可通过调节细胞增殖促进多种癌症的发展。在从石蜡包埋的癌组织中提取的DNA样本中检测了NR5A2（rs3790843和rs3790844）单核苷酸多态性（SNP）基因分型。收集了944例胃癌（GC）患者的临床病理和随访数据。使用SPSS 18.0版分析这两个SNP与胃癌患者病情进展和预后的关联。我们发现NR5A2 rs3790843多态性与发生区域淋巴结转移（p = 0.044）或远处转移（p = 0.020）的GC风险显著相关。我们还发现，rs3790844多态性与优势模型（GG与GA/AA相比，风险比（HR）= 0.823，95%置信区间（CI）= 0.679 - 0.997）中GC患者总生存期（OS）的延长相关，表明变异A等位基因具有潜在的保护作用。此外，在分层分析中，在女性组、肿瘤大小>5 cm的组中，优势模型下NR5A2 rs3790843和rs3790844多态性均与死亡风险显著降低相关。我们的研究结果首次表明，优势模型下NR5A2 rs3790844多态性与GC患者OS延长相关，并且在女性组和肿瘤大小>5 cm组中，NR5A2 rs3790843多态性也发现了类似结果。需要在其他不同种族人群的更大规模研究中进行进一步验证和功能评估。
