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miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma

Authors :
Claudio B. Murta
Tatiane K. Furuya
Alexis G. M. Carrasco
Miyuki Uno
Laura Sichero
Luisa L. Villa
Sheila F. Faraj
Rafael F. Coelho
Giuliano B. Guglielmetti
Mauricio D. Cordeiro
Katia R. M. Leite
William C. Nahas
Roger Chammas
José Pontes
Source :
International Journal of Molecular Sciences, Vol 23, Iss 13, p 7103 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

Penile cancer (PeC) is a rare disease, and no prognostic biomarkers have been adopted in clinical practice yet. The objective of the present study was to identify differentially expressed miRNAs (DEmiRs) and genes (DEGs) as potential biomarkers for lymph node metastasis and other prognostic factors in PeC. Tumor samples were prospectively obtained from 24 patients with squamous cell carcinoma of the penis. miRNA microarray analysis was performed comparing tumors from patients with inguinal lymph node metastatic and localized disease, and the results were validated by qRT-PCR. Eighty-three gene expression levels were also compared between groups through qRT-PCR. Moreover, DEmiRs and DEGs expression levels were correlated with clinicopathological variables, cancer-specific (CSS), and overall survival (OS). TAC software, TM4 MeV 4.9 software, SPSS v.25.0, and R software v.4.0.2 were used for statistical analyses. We identified 21 DEmiRs in microarray analysis, and seven were selected for validation. miR-744-5p and miR-421 were overexpressed in tissue samples of metastatic patients, and high expression of miR-421 was also associated with lower OS. We found seven DEGs (CCND1, EGFR, ENTPD5, HOXA10, IGF1R, MYC, and SNAI2) related to metastatic disease. A significant association was found between increased MMP1 expression and tumor size, grade, pathological T stage, and perineural invasion. Other genes were also associated with clinicopathological variables, CSS and OS. Finally, we found changes in mRNA–miRNA regulation that contribute to understanding the mechanisms involved in tumor progression. Therefore, we identified miRNA and mRNA expression profiles as potential biomarkers associated with lymph node metastasis and prognosis in PeC, in addition to disruption in mRNA–miRNA regulation during disease progression.

Details

Language :
English
ISSN :
14220067 and 16616596
Volume :
23
Issue :
13
Database :
Directory of Open Access Journals
Journal :
International Journal of Molecular Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.76c6d63b90e4403490f9090bb82191e4
Document Type :
article
Full Text :
https://doi.org/10.3390/ijms23137103