Association of SPOP, CHD1 and PTEN expression with recurrence in high-risk prostate cancer patients

• Grant number: 22/13507-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2023
• End date: December 31, 2023
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Sabrina Thalita dos Reis Faria
• Grantee: Giovana Vilas Boas Caetano
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Prostate cancer (PCa) is a public health issue and is considered the second most frequent type of tumor in the male population worldwide. According to INCA, in 2020, the PCa was responsible for 358,301 deaths. Screening is done preventively through PSA measurement, and diagnosis is made by biopsy. The prognosis is based on PSA dosage, pathological stage, tumor volume, and histological grade; the last one is the most important. PCa has complex genetics, and many genes and molecular alterations have already been associated with its carcinogenesis and progression. It has already been demonstrated that primary PCa has mutations in tumor suppressors, such as the SPOP, CDH1, and PTEN genes. SPOP gene promotes the degradation of oncoproteins that regulate cellular processes such as cell cycle and metabolism, invasion, and apoptosis and controls the stability of the androgen receptor (AR) protein damage related to this gene can be intensified with the deletion of CDH1, which is an adhesion and anchoring gene and is also involved in the transmission of chemical signals within cells when mutated leads to a worse prognosis. Finally, the loss of PTEN gene is associated with a worse prognosis, and its absence modifies numerous pathways that can accelerate the development of the disease. Therefore, as it is a disease with heterogeneity, it is essential to study the genes that may be associated with tumor progression, being essential for understanding the molecular basis. With this, this project proposes to evaluate the expression of CDH1, SPOP, and PTEN genes in the PCa of high risk, next to correlating the expression levels with the clinical pathological data of the patients, analyzing which patients will or will not progress to disease recurrence and biochemistry. In addition, analyzing the mutations of such games with the help of bioinformatics through databases. For this, we selected 60 patients diagnosed with PCa, who underwent surgical treatment for the disease and a control group, samples from 5 patients with benign prostatic hyperplasia (BPH) will be used. To analyze the expression levels of the genes, we will extract the total RNA from the samples using conventional extraction methods; then, we will perform the qPCR analysis using specifically for each selected gene.