Discriminative and Distinct Phenotyping by Constrained Tensor Factorization

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Perfil transcricional do gene ARID1A em células de Câncer de Próstata

Prostate cancer (CaP) is the second most common cancer among Brazilian men, after non-melanoma skin cancer. The onset and progression of this malignant neoplasm are associated with several molecular events that control the expression of different genes. The ARID1A protein is one of the subunits that confers specificity to the SWI / SNFA (BAF) chromatin remodeling complex, described as a tumor suppressor. However, its role in PCa has not yet been elucidated. In this sense, we analyzed the role of ARID1A gene transcripts in prostatic tumorigenesis by qPCR. We also correlated the expression of ARID1A with the mRNA levels of the ANXA1, AR, PSA, AR-V7 and HER2 genes. Total mRNA was extracted from LNCaP (hormone-dependent), DU145 and PC3 (hormone-independent) and non-tumorigenic RWPE-1 prostatic cell lines. The comparative Cq method was optimized to quantify the transcripts normalized by the B2M gene. The expression of ARID1A was 1.22 and 1.15 fold higher in LNCaP and PC3 lineages when compared to RWPE-1 (P0.94). The results suggest that ARID1A is involved in the onset or initial development of PCa. The loss of ANXA1 in LNCaP may be related to the tumor's genesis and the subsequent elevation of mRNA levels in DU145 and PC3 may be associated to the resistance to hormone therapy. Additional experiments are needed to evaluate the behavior of the proteins transcribed by these genes for validation of biomarkers to advanced PCa.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoTrabalho de Conclusão de Curso (Graduação)O Câncer de Próstata (CaP) é, atualmente, o segundo tipo mais frequente entre os homens brasileiros, ficando atrás somente do câncer de pele não melanoma. O surgimento e a progressão dessa neoplasia maligna estão associados a diversos eventos moleculares que controlam a expressão de diferentes genes. A proteína ARID1A é a uma das subunidades que confere especificidade ao complexo de remodelagem da cromatina SWI/SNFA (BAF), descrita como supressora tumoral. Porém, seu papel no CaP ainda não foi elucidado. Nesse sentido, avaliamos o papel dos transcritos do gene ARID1A na tumorigênese prostática por qPCR, bem como correlacionamos sua expressão com os níveis de mRNA dos genes ANXA1, AR, PSA, AR-V7 e HER2. Foram extraídos o mRNA total das linhagens tumorais prostáticas LNCaP (hormônio-dependente), DU145 e PC3 (hormônio-independentes) e da não-tumorigênica RWPE-1. Foi otimizado o método Cq comparativo a fim de avaliar os transcritos normalizados pelo gene B2M. A expressão de ARID1A foi 1,22 e 1,15 vezes maior nas linhagens LNCaP e PC3 quando comparadas à RWPE-1 (P0,94). Os resultados sugerem que ARID1A esteja envolvido no surgimento ou desenvolvimento inicial do CaP, que a perda de ANXA1 em LNCaP esteja relacionada com a gênese do tumor e sua posterior elevação em DU145 e PC3 pode estar associada à resistência a terapia hormonal. São necessários experimentos que avaliem o comportamento das proteínas produzidas por esses genes para posterior aplicação como biomarcadores direcionados ao CaP avançado

Discovery of Prostate Specific Antigen Pattern to Predict Castration Resistant Prostate Cancer of Androgen Deprivation Therapy

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Discovery of Prostate Specific Antigen Pattern to Predict Castration Resistant Prostate Cancer of Androgen Deprivation Therapy

Background: Prostate specific antigen (PSA) is an important biomarker to monitor the response to the treatment, but has not been fully utilized as a whole sequence. We used a longitudinal biomarker PSA to discover a new prognostic pattern that predicts castration-resistant prostate cancer (CRPC) after androgen deprivation therapy. Methods: We transformed the longitudinal PSA into a discrete sequence, used frequent sequential pattern mining to find candidate patterns from the sequences, and selected the most predictive and informative pattern among the candidates. Results: Patients were less likely to be CRPC if, after PSA values reach nadir, the PSA decreases more than 0.048 ng/ml during a month, and the decrease occurs again. This pattern significantly increased the accuracy of predicting CRPC by supplementing information provided by existing PSA patterns such as pretreatment PSA. Conclusions: This result can help clinicians to stratify men by the risk of CRPC and to determine the patient that needs intensive follow-up.1133Nsciescopu