State Key Laboratory of Molecular Oncology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Nat Genet. 2013 Jun;45(6):632-8. doi: 10.1038/ng.2638. Epub 2013 May 5.
We conducted a genome-wide scan of SNPs to identify variants associated with length of survival in 1,331 individuals with esophageal squamous-cell carcinoma (ESCC), with associations validated in 2 independent sets including 1,962 individuals with this cancer. We identified rs1050631 in SLC39A6 as associated with the survival times of affected individuals, with the hazard ratio for death from ESCC in the combined sample being 1.30 (95% confidence interval (CI) = 1.19-1.43; P = 3.77 × 10(-8)). rs7242481, located in the 5' UTR of SLC39A6, disturbs a transcriptional repressor binding site and results in upregulation of SLC39A6 expression. Immunohistochemical staining of ESCC tissues showed that higher expression of SLC39A6 protein was correlated with shorter length of survival in individuals with advanced ESCC (P = 0.013). Knockdown of SLC39A6 expression suppressed proliferation and invasion in ESCC cells. These results suggest that SLC39A6 has an important role in the prognosis of ESCC and may be a potential therapeutic target.
我们进行了全基因组 SNP 扫描，以鉴定与 1331 名食管鳞癌 (ESCC) 患者生存时间相关的变异，在包括 1962 名此类癌症患者的 2 个独立队列中验证了这些关联。我们在 SLC39A6 中鉴定出 rs1050631 与受影响个体的生存时间相关，在合并样本中，ESCC 死亡的风险比为 1.30（95%置信区间 (CI) = 1.19-1.43；P = 3.77×10(-8))。位于 SLC39A6 5'UTR 的 rs7242481 破坏了转录抑制因子结合位点，导致 SLC39A6 表达上调。ESCC 组织的免疫组织化学染色显示，在晚期 ESCC 患者中，SLC39A6 蛋白表达水平较高与生存时间较短相关（P = 0.013）。SLC39A6 表达的敲低抑制了 ESCC 细胞的增殖和侵袭。这些结果表明 SLC39A6 在 ESCC 的预后中具有重要作用，可能是一个潜在的治疗靶点。
