Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer.
Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer.
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DOI：
10.1186/1471-2407-14-545
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发表时间：
2014-07-28
期刊：
影响因子：
3.8
通讯作者：
Kim JH
中科院分区：
文献类型：
--
作者：
Cho H;Chung JY;Song KH;Noh KH;Kim BW;Chung EJ;Ylaya K;Kim JH;Kim TW;Hewitt SM;Kim JH
凋亡抑制因子5（apoptosis inhibitor-5，API 5）是一种抗凋亡蛋白，被认为是肿瘤进展和肿瘤细胞恶性表型的关键分子。本研究旨在探讨API 5在宫颈癌中的表达及其临床意义，以及API 5与磷酸化细胞外信号调节激酶1和2（pERK 1/2）在宫颈癌发生发展中的关系。在宫颈癌细胞系中评估API 5对细胞生长的影响。对173例原发性宫颈癌、306例宫颈上皮内瘤样病变（CIN）和429例正常宫颈组织进行API 5和pERK 1/2免疫组化染色。API 5过表达促进CaSki细胞的增殖和集落形成，而API 5敲低抑制HeLa细胞的这两种特性。免疫组化结果显示，API 5在宫颈癌组织中的表达在正常宫颈组织中逐渐增高（P < 0.001），且与宫颈癌的分期（P = 0.004）、分级（P < 0.001）和放化疗效果（P = 0.004）有关。API 5与pERK 1/2在宫颈癌和高级别CIN中的表达呈正相关（P < 0.001和P = 0.031）。多因素分析显示，API 5+（P = 0.039）和API 5 +/pERK 1/2+（P = 0.032）是影响总生存期的独立预后因素。API 5表达与宫颈癌患者亚组中的pERK 1/2相关，其表达预测总生存率较差，支持API 5可能是治疗干预的有前途的新靶点。本文的在线版本（doi：10.1186/1471-2407-14-545）包含补充材料，可供授权用户使用。
The apoptosis inhibitor-5 (API5), anti-apoptosis protein, is considered a key molecule in the tumor progression and malignant phenotype of tumor cells. Here, we investigated API5 expression in cervical cancer, its clinical significance, and its relationship with phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2) in development and progression of cervical cancer. API5 effects on cell growth were assessed in cervical cancer cell lines. API5 and pERK1/2 immunohistochemical staining were performed on a cervical cancer tissue microarray consisting of 173 primary cervical cancers, 306 cervical intraepithelial neoplasias (CINs), and 429 matched normal tissues. API5 overexpression promoted cell proliferation and colony formation in CaSki cells, whereas API5 knockdown inhibited the both properties in HeLa cells. Immunohistochemical staining showed that API5 expression increased during the normal to tumor transition of cervical carcinoma (P < 0.001), and this increased expression was significantly associated with tumor stage (P = 0.004), tumor grade (P < 0.001), and chemo-radiation response (P = 0.004). API5 expression levels were positively associated with pERK1/2 in cervical cancer (P < 0.001) and high grade CIN (P = 0.031). In multivariate analysis, API5+ (P = 0.039) and combined API5+/pERK1/2+ (P = 0.032) were independent prognostic factors for overall survival. API5 expression is associated with pERK1/2 in a subset of cervical cancer patients and its expression predicts poor overall survival, supporting that API5 may be a promising novel target for therapeutic interventions. The online version of this article (doi:10.1186/1471-2407-14-545) contains supplementary material, which is available to authorized users.
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