Pinho Jaqueline Diniz, Barros Silva Gyl Eanes, Teixeira Júnior Antonio Augusto Lima, Belfort Marta Regina de Castro, Mendes Juliana Melo Macedo, Calixto José de Ribamar Rodrigues, Nogueira Leudivan Ribeiro, Burbano Rommel Rodriguez, Khayat André Salim
University State of Maranhão, Zé Doca, MA, Brazil.
Laboratory of Imunofluorescence and Electron Microscopy, Hospital Universitário Presidente Dutra (HUUFMA), São Luís, Brazil.
Transl Androl Urol. 2021 May;10(5):2019-2026. doi: 10.21037/tau-20-1378.
Human papillomavirus (HPV) infection is a risk factor for penile cancer (PC). The miR-145 expression has been correlated to this virus genomic amplification. In this context, this work aims to determine the expression level of miR-145 in penile tumors infected by high-risk HPV and correlate it with the clinicopathological characteristics of the tumor and protein expression of p53.
Formalin-fixed paraffin-embedded from 52 patients with PC, at diagnosis and prior to any cancer treatment, were obtained. HPV identification was performed by nested type PCR, and miR-145 expression was obtained by qRT-PCR. Immunohistochemical analysis of p53 and Ki-67 was performed.
Tumoral miR-145 expression was significantly lower compared to adjacent tissue. Additionally, there was a significant reduction of miR-145 expression in invasion perineural, histological associated HPV, and absence of p53 expression in positive HPV cases. HPV infection was detected in 86.5%, the most frequent HPV16. Reduced disease-free survival was observed in patients with low expression of miR-145.
Our data suggest that the underexpression of miR-145 may be triggered by HPV action, decreasing protein expression of p53, and being correlated with perineural invasion. Therefore, the deregulation of miR-145 provides clues as to the potential role in penile carcinogenesis and is also a potential candidate for validation in noninvasive samples.
人乳头瘤病毒（HPV）感染是阴茎癌（PC）的一个风险因素。miR-145的表达与这种病毒的基因组扩增相关。在此背景下，本研究旨在确定高危HPV感染的阴茎肿瘤中miR-145的表达水平，并将其与肿瘤的临床病理特征及p53蛋白表达相关联。
获取52例PC患者在诊断时及任何癌症治疗前的福尔马林固定石蜡包埋组织。通过巢式PCR进行HPV鉴定，通过qRT-PCR获得miR-145表达。进行p53和Ki-67的免疫组织化学分析。
肿瘤组织中miR-145的表达显著低于相邻组织。此外，在神经周围浸润、组织学相关HPV感染以及HPV阳性病例中p53表达缺失的情况下，miR-145表达显著降低。86.5%的患者检测到HPV感染，最常见的是HPV16。miR-145低表达的患者无病生存期缩短。
我们的数据表明，miR-145的低表达可能由HPV作用引发，导致p53蛋白表达降低，并与神经周围浸润相关。因此，miR-145的失调为其在阴茎癌发生中的潜在作用提供了线索，也是无创样本验证的潜在候选指标。
