An MGMT Allelic Variant Can Affect Biochemical Relapse in Prostate Cancer Patients.

BACKGROUND/AIM: Prostate cancer (PCa) is one of the most frequent neoplasms in men around the world. In recent years, the search for new biomarkers with greater prognostic potential for PCa has intensified. This study aimed to evaluate single nucleotide polymorphisms (SNPs) and a combined panel of these polymorphisms in relation to biochemical recurrence in patients who were through prostatectomy, with an average of 7 years of follow-up. MATERIALS AND METHODS: Patients diagnosed with PCa (n=197) participated in this cohort study. Thirteen SNPs were analyzed: rs2279115 (BCL-2), rs26677604 (CASP3), rs1052571 (CASP9), rs11781886 (NKX3-1), rs2735343 (PTEN), rs2494750 (AKT1), rs2699887 (PI3KCA), rs3195676 (AMACR), rs17302090 (AR), rs2536 (mTOR), rs1695 (GSTP1), rs2308321 (MGMT) and rs1544410 (VDR). Variants were combined and four main panels were defined: cell death, cell survival, growth receptors, and metabolism. Genotyping was performed by real-time PCR. RESULTS: We did not observe any significant relation between the panels of variants analyzed, apart from the rare allele (G) of rs2308321 (MGMT) that was associated with a higher risk of recurrence (p=0.036) when compared to the prevalent (A) in the allelic model. CONCLUSION: This MGMT variant occurs in an exon, and it could potentially affect DNA repair and, therefore, the biochemical relapse of PCa patients.

The potential of cell-free and exosomal microRNAs as biomarkers in liquid biopsy in patients with prostate cancer.

PURPOSE: Prostate cancer (PCa) is the 4th most diagnosed cancer and the 8th leading cause of cancer-related death worldwide. Currently, clinical risk stratification models including factors like PSA levels, Gleason score, and digital rectal examination are used for this purpose. There is a need for novel biomarkers that can distinguish between indolent and aggressive pathology and reduce the risk of overdiagnosis/overtreatment. Liquid biopsy has a non-invasive character, can lead to less morbidity and provide new biomarkers, such as miRNAs, that regulate diverse important cellular processes. Here, we report an extended revision about the role of cell-free and exosomal miRNAs (exomiRNAs) as biomarkers for screening, diagnosis, prognosis, or treatment of PCa. METHODS: A comprehensive review of the published literature was conducted focusing on the usefulness, advantages, and clinical applications of cell-free and exomiRNAs in serum and plasma. Using PubMed database 53 articles published between 2012 and 2021 were selected and discussed from the perspective of their use as diagnostic, prognostic and therapeutic biomarkers for PCa. RESULTS: We identify 119 miRNAs associated with PCa development and the cell-free and exosomal miR-21, miR-141, miR-200c, and miR-375 were consistently associated with progression in multiple cohorts/studies. However, standardized experimental procedures, and well-defined and clinically relevant cohort studies are urgently needed to confirm the biomarker potential of cell-free and exomiRNAs in serum or plasma. CONCLUSION: Cell-free and exomiRNAs in serum or plasma are promising tools for be used as non-invasive biomarkers for diagnostic, prognosis, therapy improvement and clinical outcome prediction in PCa patients.

Polymorphic variants of the CASP3, CASP9, BCL-2 and NKX3-1 genes as candidate markers for prostate cancer susceptibility and poor prognosis.

BACKGROUND: There is an ongoing search for molecular markers that are specific, sensitive, and able to predict the stage of prostate cancer (PCa), which is the second most prevalent type of cancer in men worldwide. This study examined whether different single nucleotide polymorphisms (SNPs) were reliable markers of susceptibility to and prognosis of PCa in a sample of Brazilian patients. METHODS AND RESULTS: DNA samples were extracted from peripheral blood cells of 283 PCa patients and matched with samples from healthy controls. Single nucleotide polymorphisms (SNPs in four genes (BCL-2-rs2279115, CASP3-rs4647603, CASP9-rs1052571, and NKX3-1-rs11781886) were genotyped by real-time PCR using the TaqMan® probe. Odds Ratios with 95% confidence intervals were calculated for allelic and genotypic frequencies. The association between polymorphic variants, risk of developing PCa, and clinicopathological characteristics was analyzed by univariate and multivariate logistic regression analysis. SNPs in CASP3, CASP9, and NKX3-1 genes, either alone or in combination (BCL-2+NKX3-1 and CASP3+NKX3-1) were associated with the risk of developing PCa. Genotypes and tumor histopathological data indicated that the BCL-2, NKX3-1, and CASP3 allelic variants, either alone or combined in pairs, were associated with a poor prognosis of PCa. CONCLUSIONS: Genetic polymorphisms in CASP3, NKX3-1, and BCL-2 genes were associated with susceptibility to PCa. The SNPs in the three genes alone and the SNP in the BCL-2 gene combined with the other two genes were strongly associated with adverse outcomes in PCa patients and are promising candidates for molecular markers for PCa prognosis.