人乳头瘤病毒与前列腺癌：病毒表达蛋白在抑制失巢凋亡和促进转移中的作用。

Human papillomavirus and prostate cancer: The role of viral expressed proteins in the inhibition of anoikis and induction of metastasis.

机构信息

Department of Virology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Student Research Committee, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Microb Pathog. 2021 Mar;152:104576. doi: 10.1016/j.micpath.2020.104576. Epub 2020 Oct 18.

DOI:10.1016/j.micpath.2020.104576

PMID:33086103

Abstract

BACKGROUND

The aim of this study is to address the role of HPV in prostate cancer (PCa) development through the inducement of resistance to anoikis.

METHODS

In this case-control study, prostate tissues and blood samples were collected from 116 individuals, including 72 cases with PCa and 44 non-malignant prostate tissue samples as a control group. The expression level of HPV genes (E2, E6, and E7) and cellular genes including anti-apoptotic mediators (Bcl-2 and survivin), tumor suppressor proteins (Rb and p53), and some mediators involved in anoikis resistance and invasiveness (E-cadherin, N-cadherin, Twist, PTPN13 and SLUG) were evaluated.

RESULTS

HPV genome was identified in 36.1% cases and 15.9% control samples, additionally there was found to be a statistic significant association between the presence of HPV and PCa (OR = 1.64, 95% C.I = 0.8-1.8, P-value = 0.023). HPV genotype 16 and 18 were the most prevalent genotype in both in the PCa group and the control group. The expression level of the tumor suppressor proteins (Rb and p53) and anti-apoptotic mediators (Bcl-2 and Survivin) were significantly decreased and increased, respectively, in the HPV-positive specimens compared to the HPV-negative specimens. Furthermore, the mean expression level of N-cadherin, SLUG, and TWIST in the HPV-positive specimens was higher than HPV-negative specimens while the mean expression level of PTPN-13 and E-cadherin genes in the HPV-positive specimens was lower than HPV-negative specimens.

CONCLUSION

Our study suggests that HPV infection may be involved in the development of PCa metastases by modulating anoikis resistance related genes.

摘要

背景

本研究旨在通过诱导抗失巢凋亡来探讨 HPV 在前列腺癌（PCa）发展中的作用。

方法

在这项病例对照研究中，共采集了 116 例个体的前列腺组织和血样，其中包括 72 例 PCa 患者和 44 例非恶性前列腺组织样本作为对照组。评估了 HPV 基因（E2、E6 和 E7）和细胞基因的表达水平，包括抗凋亡介质（Bcl-2 和 survivin）、肿瘤抑制蛋白（Rb 和 p53）以及一些参与抗失巢凋亡和侵袭的介质（E-钙黏蛋白、N-钙黏蛋白、Twist、PTPN13 和 SLUG）。

结果

HPV 基因组在 36.1%的病例和 15.9%的对照组样本中被鉴定出来，并且 HPV 的存在与 PCa 之间存在统计学显著关联（OR=1.64，95%CI=0.8-1.8，P 值=0.023）。HPV 基因型 16 和 18 是 PCa 组和对照组中最常见的基因型。与 HPV 阴性标本相比，HPV 阳性标本中的肿瘤抑制蛋白（Rb 和 p53）和抗凋亡介质（Bcl-2 和 survivin）的表达水平显著降低和升高。此外，HPV 阳性标本中 N-钙黏蛋白、SLUG 和 TWIST 的平均表达水平高于 HPV 阴性标本，而 HPV 阳性标本中 PTPN-13 和 E-钙黏蛋白基因的平均表达水平低于 HPV 阴性标本。