Decreased expression of PinX1 protein is correlated with tumor development and is a new independent poor prognostic factor in ovarian carcinoma
Decreased expression of PinX1 protein is correlated with tumor development and is a new independent poor prognostic factor in ovarian carcinoma
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PinX1蛋白表达降低与肿瘤发生发展相关，是卵巢癌新的独立不良预后因素
DOI：
10.1111/j.1349-7006.2010.01560.x
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发表时间：
2010-06-01
期刊：
影响因子：
5.7
通讯作者：
Xie, Dan
中科院分区：
文献类型：
--
作者：
Cai, Mu-Yan;Zhang, Bin;Xie, Dan
人类相互作用蛋白 X1 (PinX1) 已被确定为一种关键的端粒酶抑制剂，并被认为是一种假定的肿瘤抑制基因。 PinX1 的缺失已在多种恶性肿瘤中被发现，但上皮性卵巢肿瘤中的表达状态尚未得到研究。在这项研究中，对上皮性卵巢肿瘤（包含 25 个囊腺瘤、29 个交界性肿瘤和 157 个浸润性癌）和 12 个正常卵巢的组织微阵列 (TMA) 进行了 PinX1 蛋白的免疫组织化学分析。使用受试者操作曲线（ROC）分析来确定肿瘤阳性的截止分数并评估患者的生存状态。根据 ROC 下面积，PinX1 阳性阈值确定为 60% 以上（曲线下面积 = 0.856，P < 0.001）。 PinX1在100%的正常卵巢组织、84%的囊腺瘤、75.9%的交界性肿瘤和66.2%的卵巢癌中观察到阳性表达。 PinX1表达的降低与淋巴结转移（P = 0.024）、远处转移（P < 0.001）和国际妇产科联合会（FIGO）分期晚期（P < 0.001）等不良预后因素密切相关。在单变量生存分析中，PinX1 缺失与患者生存缩短之间存在高度显着相关性（平均 48.2 个月 vs 99.2 个月，P<0.001）。多变量分析表明 PinX1 表达 (P = 0.027) 作为独立参数进行评估。我们的研究结果表明，PinX1 的缺失对于上皮性卵巢癌患者来说是一个不利的独立分子标志物。由于抑制端粒酶活性，PinX1 可能成为基于端粒酶的抗癌治疗的新靶点。 （癌症科学 2010）
Human interacting protein X1 (PinX1) has been identified as a critical telomerase inhibitor and proposed to be a putative tumor suppressor gene. Loss of PinX1 has been found in a large variety of malignancies, but the expression status in epithelial ovarian tumors has not been investigated. In this study, immunohistochemistry for PinX1 protein was performed on a tissue microarray (TMA) of epithelial ovarian tumors (informatively containing 25 cystadenomas, 29 borderline tumors, and 157 invasive carcinomas) and 12 normal ovaries. Receiver–operator curve (ROC) analysis was used to determine cut‐off scores for tumor positivity and to evaluate patients’ survival status. The threshold for PinX1 positivity was determined to be above 60% (area under the curve = 0.856, P < 0.001) based on the area under the ROC. Positive expression of PinX1 was observed in 100% of normal ovarian tissues, in 84% of cystadenomas, in 75.9% borderline tumors, and 66.2% of ovarian carcinomas. Decreased expression of PinX1 was strongly related to patients with poor prognostic factors regarding presence of lymph node metastasis (P = 0.024), distant metastasis (P < 0.001), and late International Federation of Gynecology and Obstetrics (FIGO) stage (P < 0.001). In univariate survival analysis, a highly significant correlation between loss of PinX1 and shortened patient survival (mean, 48.2 months vs 99.2 months, P < 0.001) was displayed. Multivariate analysis demonstrated PinX1 expression (P = 0.027) was evaluated as an independent parameter. Our findings suggest that loss of PinX1 is an adverse independent molecular marker for epithelial ovarian carcinoma patients. PinX1 may be a novel target for telomerase‐based anticancer therapy due to inhibiting telomerase activity. (Cancer Sci 2010)