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生长调节致癌基因-1、肝细胞生长因子、血小板衍生生长因子-AA和可溶性E-选择素在子宫颈鳞状细胞癌中的表达及其与高危型人乳头瘤病毒感染的关系

Expression of growth‑regulated oncogene‑1, hepatocyte growth factor, platelet‑derived growth factor‑AA and soluble E‑selectin and their association with high‑risk human papillomavirus infection in squamous cell carcinoma of the uterine cervix.

作者信息

Zhang Ye, Wu Jian-Zhong, Yang Yong-Qin, Ma Rong, Zhang Jun-Ying, Feng Ji-Feng

机构信息

Department of Chemotherapy, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.

Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital, Nanjing Medical University, Nanjing, Jiangsu 210009, P.R. China.

出版信息

Mol Med Rep. 2014 Aug;10(2):1013-24. doi: 10.3892/mmr.2014.2293. Epub 2014 Jun 2.

Abstract

The aim of the present study was to evaluate the clinical significance and prognostic value of growth‑regulated oncogene‑1 (GRO‑1), hepatocyte growth factor (HGF), platelet‑derived growth factor‑AA (PDGF‑AA), soluble E‑selectin (sE‑selectin) and high‑risk human papillomavirus (HPV; types 16, 18/45, 31 and 33/52/58/67) infection in cervical squamous cell carcinoma (CSCC). A total of 426 cases were enrolled in the present study, of which 292 cases were patients with CSCC, 43 were patients with cervical intraepithelial neoplasia (CIN) and 91 were healthy controls. Luminex xMAP technology was used to detect the serum levels of GRO‑1, HGF, PDGF‑AA and sE‑selectin in all cases and two‑channel fluorescence quantitative polymerase chain reaction was used to determine HPV DNA in cervical scrapings from CSCC and CIN patients. The results demonstrated that the serum levels of GRO‑1, HGF and sE‑selectin were significantly higher in patients with CSCC compared with patients with CIN and the healthy controls (P<0.0001). Compared with the CIN patients, the HPV positive rate in the CSCC patients significantly increased (P=0.013). The four factors were correlated with certain clinicopathological variables of CSCC patients to a certain degree (P<0.05) and the levels of HGF were closely associated with HPV infection (P=0.039). The receiver operating characteristic curves demonstrated that HGF obtained the highest diagnostic value compared with the other three factors. Multivariate Cox regression analysis demonstrated that the serum levels of HGF (P<0.0001), FIGO stage (P<0.0001) and pelvic lymph node metastasis (P=0.001) were independent prognostic factors in patients with CSCC, while high‑risk HPV infection did not show any significance in this analysis. These results demonstrated that HGF may be a useful prognostic biomarker rather than high‑risk HPV types in patients with CSCC.

摘要

本研究旨在评估生长调节致癌基因-1(GRO-1)、肝细胞生长因子(HGF)、血小板衍生生长因子-AA(PDGF-AA)、可溶性E-选择素(sE-选择素)和高危型人乳头瘤病毒(HPV;16、18/45、31和33/52/58/67型)感染在宫颈鳞状细胞癌(CSCC)中的临床意义和预后价值。本研究共纳入426例患者,其中292例为CSCC患者,43例为宫颈上皮内瘤变(CIN)患者,91例为健康对照。采用Luminex xMAP技术检测所有病例血清中GRO-1、HGF、PDGF-AA和sE-选择素水平,采用双通道荧光定量聚合酶链反应检测CSCC和CIN患者宫颈刮片中HPV DNA。结果显示,与CIN患者和健康对照相比,CSCC患者血清中GRO-1、HGF和sE-选择素水平显著升高(P<0.0001)。与CIN患者相比,CSCC患者HPV阳性率显著升高(P=0.013)。这四个因素与CSCC患者的某些临床病理变量在一定程度上相关(P<0.05),且HGF水平与HPV感染密切相关(P=0.039)。受试者工作特征曲线显示,与其他三个因素相比,HGF具有最高的诊断价值。多因素Cox回归分析显示,血清HGF水平(P<0.0001)、国际妇产科联盟(FIGO)分期(P<0.0001)和盆腔淋巴结转移(P=0.001)是CSCC患者的独立预后因素,而高危型HPV感染在该分析中无显著意义。这些结果表明,在CSCC患者中,HGF可能是一个有用的预后生物标志物,而非高危型HPV。

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