CLAUDIO BOVOLENTA MURTA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
LIM/55 - Laboratório de Urologia, Hospital das Clínicas, Faculdade de Medicina
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- miRNA and mRNA Expression Profiles Associated with Lymph Node Metastasis and Prognosis in Penile Carcinoma(2022) MURTA, Claudio B.; FURUYA, Tatiane K.; CARRASCO, Alexis G. M.; UNO, Miyuki; SICHERO, Laura; VILLA, Luisa L.; FARAJ, Sheila F.; COELHO, Rafael F.; GUGLIELMETTI, Giuliano B.; CORDEIRO, Mauricio D.; LEITE, Katia R. M.; NAHAS, William C.; CHAMMAS, Roger; PONTES JR., JosePenile 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.
- Disruption of miRNA-mRNA Networks Defines Novel Molecular Signatures for Penile Carcinogenesis(2021) FURUYA, Tatiane Katsue; MURTA, Claudio Bovolenta; CARRASCO, Alexis German Murillo; UNO, Miyuki; SICHERO, Laura; VILLA, Luisa Lina; CARDILLI, Leonardo; COELHO, Rafael Ferreira; GUGLIELMETTI, Giuliano Betoni; CORDEIRO, Mauricio Dener; LEITE, Katia Ramos Moreira; NAHAS, William Carlos; CHAMMAS, Roger; JR, Jose PontesSimple Summary: As there are still no biomarkers reported in clinical practice in penile cancer (PeC), we aimed to investigate and validate molecular signatures based on miRNA and mRNA profiles to identify molecular drivers and pathways involved in PeC tumorigenesis. We found eight DEmiRs and 37 DEGs comparing tumoral tissues (TT) paired with non-neoplastic tissues (NNT) of PeC patients. Four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) were identified as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. Furthermore, we performed an analysis of miRNA-mRNA interaction and found disruption in the dynamics of the regulation of eight pairs during tumor development that have never been described in PeC. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis. Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort (n = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (IL1A, MCM2, MMP1, MMP12, SFN and VEGFA) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.