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

机译:E6p53p16MDM2和Gal-3参与宫颈癌患者的临床预后

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摘要

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.
机译:高危型人乳头瘤病毒(HPV)是宫颈癌的主要原因。 HPV癌基因负责恶性肿瘤的发展,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的上调。但是,未鉴定的蛋白质也可能在宫颈癌的发生和发展中起作用。因此,本研究的目的是分析宫颈癌标本中E6,p53,p16,MDM2原癌基因(MDM2)和galectin-3(gal-3)的表达水平。总共使用了250个宫颈癌组织玻片。 E6,p53,p16,MDM2和gal-3的表达采用免疫组织化学方法和半定量评分法进行分析。 SPSS软件用于宫颈癌患者的染色结果的统计评估和生存分析。宫颈癌标本显示E6染色显着增加,伴有晚期T状态,国际妇产科联合会分类也有所增加。与腺癌相比,E6,p53和p16在鳞状上皮组织中表现出明显不同的表达水平。 MDM2和gal-3在宫颈癌中显示出正相关的表达水平。此外,在p16阴性病例中gal-3表达与不良预后相关。在宫颈癌中,还发现E6的表达与p53的突变形式之间呈负相关。事实证明,p53突变在宫颈癌中很常见,而gal-3和MDM2似乎在这种类型的肿瘤中起联合作用。由于gal-3在预后较差的子宫颈癌组织中过表达,因此在以后的研究中应研究gal-3抑制剂的使用。

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