Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

<p>Abstract</p> <p>Background</p> <p>Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival.</p> <p>Methods</p> <p>A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers.</p> <p>Results</p> <p>A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively) or with other cancers (10, 19, and 15 genes, respectively) and the rest (16, 4, and 10 genes, respectively) are novel associations. <it>Pik3r1</it>, <it>E2f3, Akr1c3</it>, <it>Csf1</it>, <it>Jag2</it>, <it>Plcg1</it>, <it>Rpl37a</it>, <it>Sod2</it>, <it>Topors</it>, <it>Hras</it>, <it>Mdm2, Camk2g</it>, <it>Fstl1</it>, <it>Il13ra1</it>, <it>Mtap </it>and <it>Tp53 </it>were associated with multiple survival events.</p> <p>Most genes (from 90 to 96%) were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for <it>Syne1</it>, <it>Pdcd4</it>, <it>Ighg1</it>, <it>Tgfa</it>, <it>Pla2g7</it>, and <it>Paics</it>. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. <it>C2</it>, <it>Egfr</it>, <it>Prkcb</it>, <it>Igf2bp3</it>, and <it>Gdf10 </it>had gender-dependent associations; <it>Sox10</it>, <it>Rps20</it>, <it>Rab31</it>, and <it>Vav3 </it>had race-dependent associations; <it>Chi3l1</it>, <it>Prkcb</it>, <it>Polr2d</it>, and <it>Apool </it>had therapy-dependent associations. Biological processes associated glioblastoma survival included morphogenesis, cell cycle, aging, response to stimuli, and programmed cell death.</p> <p>Conclusions</p> <p>Known biomarkers of glioblastoma survival were confirmed, and new general and clinical-dependent gene profiles were uncovered. The comparison of biomarkers across glioblastoma phases and functional analyses offered insights into the role of genes. These findings support the development of more accurate and personalized prognostic tools and gene-based therapies that improve the survival and quality of life of individuals afflicted by glioblastoma multiforme.</p

Avaliação do modelo de predição clínica de Wells et al. no diagnóstico da trombose venosa profunda dos membros inferiores Evaluation of a clinical prediction model by Wells et al. in the diagnosis of deep venous thrombosis of the lower limbs

CONTEXTO: A aplicação de uma estratégia baseada em um modelo clínico associado ao mapeamento dúplex (MD) pode permitir um diagnóstico da trombose venosa profunda (TVP) mais seguro, eficaz e custo-efetivo. OBJETIVO: Testar o modelo clínico de Wells et al. associado ao MD e verificar a ocorrência de TVP nos pacientes categorizados quanto à probabilidade de apresentar a doença, e determinar se, a partir dos resultados obtidos, seria possível reduzir o número de exames seriados com o MD. MÉTODOS: Os pacientes com suspeita clínica de TVP foram categorizados quanto à apresentação de TVP em baixa, moderada e alta probabilidade (BP, MP, AP) e, em seguida, submetidos ao MD. Pacientes com MD negativo repetiram o exame em 24-48 horas e em 7 dias. Pacientes com exame positivo para TVP foram tratados. Todos os pacientes sem TVP foram convocados para reavaliação clínica em 3 meses. RESULTADOS: A ocorrência de TVP entre os 489 pacientes avaliados foi de 39,1% (191), sendo 35,6% identificados no exame inicial e 3,5% no exame seriado. Os índices de pacientes que apresentaram TVP foram de 6,1% no grupo de BP, 26,9% no grupo de MP e 79,5% no grupo de AP. No exame seriado, o percentual de TVP foi de 2,4, 7,8 e 15,1% nos grupos BP, MP e AP, respectivamente. Dos pacientes com MD negativo, 62,4% compareceram após 3 meses, e piora dos sintomas foi apresentada por apenas um paciente. Neste, o MD mostrou TVP de veia poplítea. CONCLUSÃO: Os resultados obtidos sugerem que, para os pacientes com BP para TVP e MD negativo, seria possível prescindir do exame seriado, devido à baixa ocorrência de TVP neste grupo, tornando, assim, a abordagem diagnóstica mais simples.<br>BACKGROUND: The application of a diagnostic strategy based on a clinical model associated with duplex scanning (DS) may allow for a safer and more effective/cost-effective diagnosis of deep venous thrombosis (DVT). OBJECTIVE: To evaluate the clinical model proposed by Wells et al. associated with DS and verify the occurrence of DVT in patients divided into probability of presenting the disease, and assess the possibility of reducing the number of repeated DS based on the results obtained. METHODS: Suspected DVT patients were accordingly categorized into groups of low, moderate and high DVT probability (LP, MP and HP). The patients were then submitted to DS and those without DVT were rescheduled to repeat the examination in 24-48 hours and in 7 days. Patients positively diagnosed with DVT received proper treatment. All patients without DVT were summoned to return within 3 months. RESULTS: The incidence of DVT among all 489 patients was 39.1% (191); of these, 35.6% were identified in the first examination and 3.5% in the follow-up. Among patients categorized as LP the occurrence was 6.1%, 26.9% in the MP group and 79.5% in the HP group. On the follow-up exams the incidence of DVT in LP, MP and HP groups was 2.4, 7.8 e 13.2%, respectively. Among patients with negative DS, 62.4% attended the reevaluation in 3 months and only one presented worsening of symptoms. This patient was then diagnosed with popliteal DVT using DS. CONCLUSION:The results suggest that for patients with LP for DVT and negative DS, follow-up exams are not needed, since the occurrence of DVT was low in this group. This procedure simplifies the diagnostic process