Urology Department, Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo CEP 01246-000, SP, Brazil.
Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo CEP 01246-000, SP, Brazil.
Int J Mol Sci. 2022 Jun 26;23(13):7103. doi: 10.3390/ijms23137103.
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 (, , , , , , and ) related to metastatic disease. A significant association was found between increased 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.
阴茎癌（PeC）是一种罕见疾病，目前尚未在临床实践中采用任何预后生物标志物。本研究的目的是鉴定差异表达的 microRNA（DEmiR）和基因（DEG），作为 PeC 淋巴结转移和其他预后因素的潜在生物标志物。前瞻性地从 24 例阴茎鳞状细胞癌患者中获得肿瘤样本。通过比较腹股沟淋巴结转移和局部疾病患者的肿瘤，进行 miRNA 微阵列分析，并通过 qRT-PCR 进行验证。通过 qRT-PCR 还比较了两组 83 个基因表达水平。此外，DEmiR 和 DEG 的表达水平与临床病理变量、癌症特异性（CSS）和总生存期（OS）相关。使用 TAC 软件、TM4 MeV 4.9 软件、SPSS v.25.0 和 R 软件 v.4.0.2 进行统计分析。我们在微阵列分析中鉴定了 21 个 DEmiR，其中 7 个用于验证。miR-744-5p 和 miR-421 在转移性患者的组织样本中表达上调，miR-421 的高表达也与较低的 OS 相关。我们发现 7 个与转移性疾病相关的 DEG（,,,,,, 和 ）。表达增加与肿瘤大小、分级、病理 T 分期和神经周围侵犯显著相关。其他基因也与临床病理变量、CSS 和 OS 相关。最后，我们发现了与肿瘤进展相关的 mRNA-miRNA 调控变化。因此，我们确定了 miRNA 和 mRNA 表达谱作为与 PeC 淋巴结转移和预后相关的潜在生物标志物，此外，在疾病进展过程中还存在 mRNA-miRNA 调控的破坏。
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