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MIR-107、MIR-223-3P和MIR-21-5P揭示阴茎癌潜在生物标志物

MIR-107, MIR-223-3P and MIR-21-5P Reveals Potential Biomarkers in Penile Cancer.

作者信息

Pinho Jaqueline Diniz, Silva Gyl Eanes Barros, Teixeira Júnior Antonio Augusto Lima, Belfort Marta Regina de Castro, Mendes Juliana Melo, Cunha Isabela Wernerck da, Quintana Luciana Gonçalves, Calixto José de Ribamar Rodrigues, Nogueira Leudivan Ribeiro, Coelho Ronald Wagner Pereira, Khayat André Salim

机构信息

Nucleus of Oncology Research, University Hospital João de Barros Barreto, Belém, PA, Brazil.

Department of Pathology, Ribeirão Preto Medical of School. University of Sao Paulo. Sao Paulo, Brazil.

出版信息

Asian Pac J Cancer Prev. 2020 Feb 1;21(2):391-397. doi: 10.31557/APJCP.2020.21.2.391.

Abstract

BACKGROUND

Inguinal lymph node involvement is the main prognostic factor in patients with penile cancer. However, there is a lack of marker/s for lymph node metastasis. microRNAs have been investigated as potential markers for prognosis of various types of cancer. Taking this into consideration, our main goal was to determine the association of miR-223-3p, miR-107, and miR-21-5p expression with clinicopathological characteristics, as well as presence of lymph node metastasis in patients with penile cancer.

METHODS

Formalin-fixed paraffin-embedded penile squamous cell carcinoma specimens from 50 patients, at diagnosis and prior to any cancer treatment, were obtained. Tissue samples comprising at least 70% malignant cells and adjacent non-tumor tissues were evaluated by using qRT-PCR for expression level of miR-223-3p, miR-107 and miR-21-5p. Additionally, molecular identification of HPV was performed by PCR, and the expression levels of PTEN were analyzed by immunohistochemistry.

RESULTS

Penile squamous cell carcinoma primary tumors presented higher expression of miR-223-3p, miR-107, and miR-21-5p when compared to non-tumor adjacent tissues. Upregulation of miR-223-3p was associated lymph node metastasis. Higher expression of miR-107 was associated with worsening of prognosis (as observed by histological grade II and III, tumors bigger than 2.0 cm, stage III and IV, and lower disease-free survival). In addition, higher expression of miR-107 and miR-21-5p was correlated to the absence of PTEN protein expression.

CONCLUSIONS

Our data demonstrate that higher expression of miR-223-3p, miR-107, and miR-21-5p is correlated with poor prognosis in penile cancer. The upregulation of these microRNAs potentially affect critical cancer pathways and may be important for the prognosis and response to therapy in penile cancer.

摘要

背景

腹股沟淋巴结受累是阴茎癌患者的主要预后因素。然而,目前缺乏用于淋巴结转移的标志物。微小RNA已被研究作为各种类型癌症预后的潜在标志物。考虑到这一点,我们的主要目标是确定miR-223-3p、miR-107和miR-21-5p表达与阴茎癌患者临床病理特征以及淋巴结转移情况之间的关联。

方法

获取50例阴茎鳞状细胞癌患者在诊断时且未接受任何癌症治疗之前的福尔马林固定石蜡包埋标本。使用qRT-PCR评估包含至少70%恶性细胞的组织样本以及相邻非肿瘤组织中miR-223-3p、miR-107和miR-21-5p的表达水平。此外,通过PCR进行HPV的分子鉴定,并通过免疫组织化学分析PTEN的表达水平。

结果

与相邻非肿瘤组织相比,阴茎鳞状细胞癌原发肿瘤中miR-223-3p、miR-107和miR-21-5p表达更高。miR-223-3p的上调与淋巴结转移相关。miR-107的高表达与预后恶化相关(如组织学二级和三级、肿瘤大于2.0 cm、III期和IV期以及较低的无病生存率)。此外,miR-107和miR-21-5p的高表达与PTEN蛋白表达缺失相关。

结论

我们的数据表明,miR-223-3p、miR-107和miR-21-5p的高表达与阴茎癌预后不良相关。这些微小RNA的上调可能影响关键的癌症通路,并且可能对阴茎癌的预后和治疗反应具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0c/7332144/295137a87148/APJCP-21-391-g001.jpg

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