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E6、p53、p16、MDM2和Gal-3在宫颈癌患者临床结局中的作用。

The involvement of E6, p53, p16, MDM2 and Gal-3 in the clinical outcome of patients with cervical cancer.

作者信息

Stiasny Annika, Freier Christoph P, Kuhn Christina, Schulze Sandra, Mayr Doris, Alexiou Christoph, Janko Christina, Wiest Irmi, Dannecker Christian, Jeschke Udo, Kost Bernd P

机构信息

Department of Obstetrics and Gynecology, Ludwig-Maximilians-University of Munich, D-80337 Munich, Germany.

Department of Pathology, Ludwig-Maximilians-University of Munich, D-80337 Munich, Germany.

出版信息

Oncol Lett. 2017 Oct;14(4):4467-4476. doi: 10.3892/ol.2017.6752. Epub 2017 Aug 14.

Abstract

High-risk human papilloma virus (HPV) is the leading cause of cervical cancer. HPV oncogenes are responsible for the development of malignancy, and the E6 oncoprotein that HPV expresses induces the degradation of tumour suppressor protein p53 (p53). This degradation leads to the upregulation of p16; however, unidentified proteins may also serve a role in the development and progression of cervical cancer. Therefore, the aim of the present study was to analyse the expression levels of E6, p53, p16, MDM2 proto-oncogene (MDM2) and galectin-3 (gal-3) in cervical cancer specimens. A total of 250 cervical cancer tissue slides were used. The expression of E6, p53, p16, MDM2 and gal-3 was analysed with immunohistochemical methods and a semi-quantitative scoring. SPSS software was used for the statistical evaluation of staining results and survival analysis of patients with cervical cancer. Cervical cancer specimens demonstrated significantly increased E6 staining with advanced T-status and increased International Federation of Gynecology and Obstetrics classification. E6, p53 and p16 demonstrated significantly different expression levels in squamous epithelial tissue compared with adenocarcinomas. MDM2 and gal-3 demonstrated positively correlated expression levels in cervical cancer. In addition, gal-3 expression was correlated with poor prognosis in p16-negative cases. A negative correlation between the expression of E6 and a mutated form of p53 was also identified in cervical cancer. p53 mutation was demonstrated to be common in cervical cancer, and gal-3 and MDM2 appeared to act in a combined manner in this type of tumour. As gal-3 is overexpressed in the cervical cancer tissue of patients with poor prognosis, the use of gal-3 inhibitors should be investigated in future studies.

摘要

高危型人乳头瘤病毒(HPV)是宫颈癌的主要病因。HPV癌基因与恶性肿瘤的发生发展有关,HPV表达的E6癌蛋白可诱导肿瘤抑制蛋白p53(p53)降解。这种降解导致p16上调;然而,未明确的蛋白质可能也在宫颈癌的发生发展中起作用。因此,本研究旨在分析E6、p53、p16、MDM2原癌基因(MDM2)和半乳糖凝集素-3(gal-3)在宫颈癌标本中的表达水平。共使用了250张宫颈癌组织切片。采用免疫组化方法和半定量评分分析E6、p53、p16、MDM2和gal-3的表达。使用SPSS软件对染色结果进行统计学评估,并对宫颈癌患者进行生存分析。宫颈癌标本显示,随着T分期进展和国际妇产科联盟(FIGO)分期增加,E6染色显著增加。与腺癌相比,E6、p53和p16在鳞状上皮组织中的表达水平存在显著差异。MDM2和gal-3在宫颈癌中的表达水平呈正相关。此外,在p16阴性病例中,gal-3表达与预后不良相关。在宫颈癌中还发现E6表达与p53突变形式呈负相关。p53突变在宫颈癌中很常见,gal-3和MDM2在这类肿瘤中似乎以联合方式发挥作用。由于gal-3在预后不良患者的宫颈癌组织中过表达,未来研究应探讨使用gal-3抑制剂的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a10/5649573/206197c70c33/ol-14-04-4467-g00.jpg

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