Associação da expressão de genes moduladores da inflamação com dados clínicos de pacientes com câncer de pênis

Abstract

Abstract Squamous cell carcinoma of the penis (SCCP) primarily affects men in developing countries, but an increase in cases has also been observed in developed nations. In Brazil, the state of Maranhão has the highest incidence, being considered one of the highest in the world. In its complexity, risk factors include low socioeconomic status, presence of sexually transmitted infections (STIs), human papillomavirus (HPV) infection, phimosis, chronic inflammation, and smoking. This study aims to evaluate the expression of genes associated with inflammation in tumor tissues and adjacent non-tumor tissues of patients with SCCP. Samples were collected from 11 patients who underwent penectomy, totaling 22 samples (tumor tissue and adjacent non-tumor tissue). The samples were stored in RNA latterTM and kept at -80°C until DNA extraction for viral detection and genotyping by Multiplex PCR and Nested PCR. RNA was extracted for analysis of inflammatory gene expression by RT-PCR. The sociodemographic profile showed that most individuals had low educational attainment, lived in rural areas of the state, and had a mean age of 61.45 years. In HPV detection, initially, 54.5% of the samples were positive for HPV, with the most frequent subtypes being 6, 43, and 40, and the less frequent ones being 16, 42, 50, and 72. The negative samples (n = 7 patients) were reanalyzed using Nested PCR, with 6 patients testing positive in at least one of the tissue samples, resulting in 81.8% of the samples testing positive for HPV. Gene expression analysis showed higher expression of inflammatory genes in tumor tissue compared to adjacent tissue. However, no correlation with patient staging was observed. A correlation was found between NFKB expression and age, presence of phimosis, and IL17. The TGFB pathway gene showed correlation with patient age. Expression profiles varied among patients, but TGF-β, IFN, and NFκB genes were overexpressed. When subdividing tissue samples into HPV-positive and HPV-negative in both tumor and adjacent tissues, greater expression of NFKB and TGFB was observed in HPV-positive tumor tissues. Preliminary data reinforce the relevance of HPV in penile carcinogenesis, and the analysis of inflammatory genes contributes to understanding tumor mechanisms and identifying potential therapeutic targets.