Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi'an 710032, PR China.
Department of Obstetrics and Gynecology, Xijing Hospital, Fourth Military Medical University, No. 17 Changle West Road, Xi'an 710032, PR China.
Gene. 2014 Aug 1;546(1):117-23. doi: 10.1016/j.gene.2013.07.049. Epub 2013 Aug 7.
Intercellular adhesion molecule-1 (ICAM-1, encoded by ICAM-1) is implicated in tumorigenesis and tumor progression. ICAM-1 modulates the susceptibility to several types of cancer and the disease prognosis; however, its role in epithelial ovarian cancer (EOC) is unclear. Here, we evaluate single nucleotide polymorphisms (SNPs) in ICAM-1 as predictors of EOC risk and prognosis. Six ICAM-1 polymorphisms were genotyped in 408 patients with EOC and 520 controls using the MassARRAY system. The ICAM-1 mRNA levels in 89 EOC tissues and 35 normal ovarian tissues were examined using quantitative PCR. The ICAM-1 rs5498 G allele was associated with increased tumor grade (OR=2.650) and EOC risk (OR=1.405). This risk was more evident in females who had first-degree relatives (FDRs) with a tumor (OR=3.475) or who experienced early menarche (OR=2.774). The ICAM-1 expression in the cancerous tissue was elevated compared with that of normal ovarian tissues (p<0.0001), and it was associated with an rs5498 genotype (p=0.0002). ICAM-1 SNPs did not significantly predict the overall EOC survival (p>0.05). However, the rs5498 G allele correlated with EOC survival time in patients whose FDRs suffered from a tumor (p=0.001). ICAM-1 rs5498 likely confers a high risk for EOC in G allele carriers accompanied by up-regulation of ICAM-1 expression during carcinogenesis. The combination of ICAM-1 rs5498 and tumor history predicts the EOC prognosis.
细胞间黏附分子-1(ICAM-1,由 ICAM-1 编码)参与肿瘤发生和肿瘤进展。ICAM-1 调节几种类型癌症的易感性和疾病预后;然而,其在卵巢上皮癌(EOC)中的作用尚不清楚。在这里,我们评估了 ICAM-1 中的单核苷酸多态性(SNP)作为 EOC 风险和预后的预测因子。使用 MassARRAY 系统在 408 名 EOC 患者和 520 名对照中对 6 个 ICAM-1 多态性进行了基因分型。使用定量 PCR 检测 89 个 EOC 组织和 35 个正常卵巢组织中的 ICAM-1 mRNA 水平。ICAM-1 rs5498 G 等位基因与肿瘤分级升高(OR=2.650)和 EOC 风险增加(OR=1.405)相关。这种风险在有一级亲属(FDR)患有肿瘤(OR=3.475)或初潮早(OR=2.774)的女性中更为明显。与正常卵巢组织相比,癌组织中的 ICAM-1 表达升高(p<0.0001),并且与 rs5498 基因型相关(p=0.0002)。ICAM-1 SNP 对 EOC 总生存率没有显著预测作用(p>0.05)。然而,rs5498 G 等位基因与 FDR 患有肿瘤的患者的 EOC 生存时间相关(p=0.001)。ICAM-1 rs5498 可能在携带 G 等位基因的个体中赋予 EOC 高风险,同时在癌变过程中上调 ICAM-1 表达。ICAM-1 rs5498 与肿瘤史的组合预测了 EOC 的预后。