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

Document Type: Research Articles

Authors

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

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

3 Laboratory Immunofluorescence and Electron Microscopy, University Hospital Universitário Presidente Dutra, São Luís, MA, Brazil.

4 Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, São Luís, MA, Brazil.

5 Antônio Prudente Foundation, São Paulo, Brazil.

6 Department of Medicine II, Federal University of Maranhão, São Luís, MA, Brazil.

7 Urologist at the Maranhense Institute of Oncology Aldenora Belo, Sao Luis, MA, Brazil.

8 Oncologist, Maranhense Institute of Oncology Aldenora Belo, Sao Luis, MA, Brazil.

9 Institute of Biological Sciences, Federal University of Pará, Belém, PA, Brazil.

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.

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