GABRIELA RESENDE VIEIRA DE SOUSA
Projetos de Pesquisa
Unidades Organizacionais
LIM/42 - Laboratório de Hormônios e Genética Molecular, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- DAX1 Overexpression in Pediatric Adrenocortical Tumors: A Synergic Role with SF1 in Tumorigenesis(2015) SOUSA, G. R. V. de; SOARES, I. C.; FARIA, A. M.; DOMINGUES, V. B.; WAKAMATSU, A.; LERARIO, A. M.; ALVES, V. A. F.; ZERBINI, M. C. N.; MENDONCA, B. B.; FRAGOSO, M. C. B. V.; LATRONICO, A. C.; ALMEIDA, M. Q.DAX1 transcription factor is a key determinant of adrenogonadal development, acting as a repressor of SF1 targets in steroidogenesis. It was recently demonstrated that DAX1 regulates pluripotency and differentiation in murine embryonic stem cells. In this study, we investigated DAX1 expression in adrenocortical tumors (ACTs) and correlated it with SF1 expression and clinical parameters. DAX1 and SF1 protein expression were assessed in 104 ACTs from 34 children (25 clinically benign and 9 malignant) and 70 adults (40 adenomas and 30 carcinomas). DAX1 gene expression was studied in 49 ACTs by quantitative real-time PCR. A strong DAX1 protein expression was demonstrated in 74% (25 out of 34) and 24% (17 out of 70) of pediatric and adult ACTs, respectively ((2)=10.1, p=0.002). In the pediatric group, ACTs with a strong DAX1 expression were diagnosed at earlier ages than ACTs with weak expression [median 1.2 (range, 0.5-4.5) vs. 2.2 (0.9-9.4), p=0.038]. DAX1 expression was not associated with functional status in ACTs. Interestingly, a positive correlation was observed between DAX1 and SF1 protein expression in both pediatric and adult ACTs (r=0.55 for each group separately; p<0.0001). In addition, DAX1 gene expression was significantly correlated with SF1 gene expression (p<0.0001, r=0.54). In conclusion, DAX1 strong protein expression was more frequent in pediatric than in adult ACTs. Additionally, DAX1 and SF1 expression positively correlated in ACTs, suggesting that these transcription factors might cooperate in adrenocortical tumorigenesis.
- Expression of LIN28 and its regulatory microRNAs in adult adrenocortical cancer(2015) FARIA, Andre M.; SBIERA, Silviu; RIBEIRO, Tamaya C.; SOARES, Ibere C.; MARIANI, Beatriz M. P.; FREIRE, Daniel S.; SOUSA, Gabriela R. V. de; LERARIO, Antonio M.; RONCHI, Cristina L.; DEUTSCHBEIN, Timo; WAKAMATSU, Alda; ALVES, Venancio A. F.; ZERBINI, Maria Claudia N.; MENDONCA, Berenice B.; FRAGOSO, Maria Candida B. V.; LATRONICO, Ana Claudia; FASSNACHT, Martin; ALMEIDA, Madson Q.ObjectiveLIN28 control cells reprogramming and pluripotency mainly through miRNA regulation and has been overexpressed in many advanced cancers. In this study, we evaluated the prognostic role of LIN28 and its regulatory miRNAs in a large cohort of adrenocortical tumours (ACTs). Patients and methodsLIN28 protein expression was assessed in 266 adults ACTs (78 adenomas and 188 carcinomas) from Brazil and Germany. LIN28A and LIN28B gene expression was analysed in 59 ACTs (31 adenomas and 28 carcinomas) and copy number variation in 39 ACTs. In addition, we determined the expression of let-7 family, mir-9, mir-30 and mir-125 in 28 carcinomas. ResultsLIN28A gene was overexpressed in aggressive ACCs when compared with adenomas and nonaggressive ACCs, but no LIN28A copy number variation was found in ACTs. Unexpectedly, weak LIN28 protein expression was significantly associated with reduced disease-free survival in ACC patients (P=001), but for overall survival only a trend was detectable (P=0117). In the multivariate analysis, only Ki67 index 10% (HR 46, P=0000) and weak LIN28 protein expression (HR 20, P=003) were independent predictors of recurrence in ACC patients. Interestingly, mir-9 expression, a negative LIN28A/B regulator, was significantly higher in aggressive than in nonaggressive ACCs [2076 (from 36 to 9307) vs 1334 (from 24 to 5193); P=0011] and was highly associated with reduced overall (P=001) and disease-free survival (P=001). However, mir-9 prognostic role should be further evaluated in a larger cohort. ConclusionWeak LIN28 protein expression was associated with recurrence in ACCs. Additionally, overexpression of mir-9, a negative LIN28A regulator, was associated with poor outcome.
conferenceObject Mutation and Expression Analysis of DICER1 and Mir-103 in Pediatric and Adult Adrenocortical Tumors(2014) SOUSA, Gabriela R. V.; RIBEIRO, Tamaya C.; FARIA, Andre M.; MARIANI, Beatriz M. P.; LERARIO, Antonio M.; ZERBINI, Maria Claudia N.; SOARES, Ibere C.; WAKAMATSU, Alda; ALVES, Venancio A. F.; MENDONCA, Berenice B.; FRAGOSO, Maria Candida B. V.; LATRONICO, Ana Claudia; ALMEIDA, Madson Q.conferenceObject The Specific p.R337H TP53 Germline Mutation in Adults with Adrenocortical Carcinoma(2014) GRUETZMACHER, Christiane; NAKAGUMA, Marilena; MIRANDA, Mirela Costa de; MERMEJO, Livia Mara; CASTRO, Margaret; RESENDE, Gabriela; LERARIO, Antonio M.; MENDONCA, Berenice B.; LATRONICO, Ana Claudia; ANTONINI, Sonir Roberto; ALMEIDA, Madson Q.; FRAGOSO, Maria Candida B. V.- Prognostic value of DICER1 expression in adrenocortical cancer patients(2015) SOUSA, Gabriela Resende V. de; RIBEIRO, Tamaya C.; FARIA, Andre M.; MARIANI, Beatriz M. P.; LERARIO, Antonio M.; SOARES, Ibere C.; ZERBINI, Maria Claudia N.; WAKAMATSU, Alda; ALVES, Venancio A. F.; MENDONCA, Berenice B.; FRAGOSO, Maria Candida B. V.; LATRONICO, Ana Claudia; ALMEIDA, Madson
conferenceObject High Frequency of Subclinical Cushing's Syndrome in the Inherited Autosomal Dominant Primary Macronodular Adrenal Hyperplasia Due to ARMC5 Mutations(2014) ALENCAR, Guilherme Asmar; ALMEIDA, Madson Q.; LERARIO, Antonio Marcondes; RESENDE, Gabriela; NISHI, Mirian Yumie; PEREIRA, Maria Adelaide Albergaria; MENDONCA, Berenice B.; FRAGOSO, Maria Candida B. V.article 17 Citação(ões) na Scopus Low DICER1 expression is associated with poor clinical outcome in adrenocortical carcinoma(2015) SOUSA, Gabriela Resende Vieira de; RIBEIRO, Tamaya C.; FARIA, Andre M.; MARIANI, Beatriz M. P.; LERARIO, Antonio M.; ZERBINI, Maria Claudia N.; SOARES, Ibere C.; WAKAMATSU, Alda; ALVES, Venancio A. F.; MENDONCA, Berenice B.; FRAGOSO, Maria Candida B. V.; LATRONICO, Ana Claudia; ALMEIDA, Madson Q.Low DICER1 expression was associated with poor outcome in several cancers. Recently, hot-spot DICER1 mutations were found in ovarian tumors, and TARBP2 truncating mutations in tumor cell lines with microsatellite instability. In this study, we assessed DICER1 e TRBP protein expression in 154 adult adrenocortical tumors (75 adenomas and 79 carcinomas). Expression of DICER1 and TARBP2 gene was assessed in a subgroup of 61 tumors. Additionally, we investigated mutations in metal biding sites located at the RNase IIIb domain of DICER1 and in the exon 5 of TARBP2 in 61 tumors. A strong DICER1 expression was demonstrated in 32% of adenomas and in 51% of carcinomas (p = 0.028). Similarly, DICER1 gene overexpression was more frequent in carcinomas (60%) than in adenomas (23%, p = 0.006). But, among adrenocortical carcinomas, a weak DICER1 expression was significantly more frequent in metastatic than in non-metastatic adrenocortical carcinomas (66% vs. 31%; p = 0.002). Additionally, a weak DICER1 expression was significantly correlated with a reduced overall (p = 0.004) and disease-free (p = 0.005) survival. In the multivariate analysis, a weak DICER1 expression (p = 0.048) remained as independent predictor of recurrence. Regarding TARBP2 gene, its protein and gene expression did not correlate with histopathological and clinical parameters. No variant was identified in hot spot areas of DICER1 and TARBP2. In conclusion, a weak DICER1 protein expression was associated with reduced disease-free and overall survival and was a predictor of recurrence in adrenocortical carcinomas.