Dataset Information

TCF21/POD-1, a Transcritional Regulator of SF-1/NR5A1, as a Potential Prognosis Marker in Adult and Pediatric Adrenocortical Tumors.

ABSTRACT: With recent progress in understanding the pathogenesis of adrenocortical tumors (ACTs), identification of molecular markers to predict their prognosis has become possible. Transcription factor 21 (TCF21)/podocyte-expressed 1 (POD1) is a transcriptional regulatory protein expressed in mesenchymal cells at sites of epithelial-mesenchymal transition during the development of different systems. Adult carcinomas express less TCF21 than adenomas, in addition, the KEGG pathway analysis has shown that BUB1B, among others genes, is negatively correlated with TCF21 expression. The difference between BUB1B and PTEN-induced putative kinase 1 (PINK1) expression has been described previously to be associated with survival in adult but not in pediatric carcinomas. Here, we analyzed the gene expression of TCF21, BUB1B, PINK1, and NR5A1 in adult and pediatric ACTs. We found a negative correlation between the relative expression levels of TCF21 and BUB1B in adult ACTs, but the relative expression levels of TCF21, BUB1B, PINK1, and NR5A1 were similar in childhood ACTs. In addition, we propose using the subtracted expression levels of the TCF21/POD-1 genes as a predictor of overall survival (OS) in adult carcinomas and TCF21-NR5A1 as a predictor of malignancy for pediatric tumors in patients aged <5?years. These results require further validation in different cohorts of both adult and pediatric samples. Finally, we observed that the OS for patients aged <5?years was markedly favorable compared with that for patients >5?years as well as adult patients with carcinoma. In summary, we propose TCF21/POD-1 as a new prognostic marker in adult and pediatric ACTs.

SUBMITTER: Passaia BDS

PROVIDER: S-EPMC5827685 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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TCF21/POD-1, a Transcritional Regulator of SF-1/NR5A1, as a Potential Prognosis Marker in Adult and Pediatric Adrenocortical Tumors.

Passaia Barbara Dos Santos BDS Dias Matheus Henrique MH Kremer Jean Lucas JL Antonini Sonir Roberto Rauber SRR de Almeida Madson Queiroz MQ Fragoso Maria Candida Barisson Villares MCBV Lotfi Claudimara Ferini Pacicco CFP

Frontiers in endocrinology 20180222

With recent progress in understanding the pathogenesis of adrenocortical tumors (ACTs), identification of molecular markers to predict their prognosis has become possible. Transcription factor 21 (TCF21)/podocyte-expressed 1 (POD1) is a transcriptional regulatory protein expressed in mesenchymal cells at sites of epithelial-mesenchymal transition during the development of different systems. Adult carcinomas express less <i>TCF21</i> than adenomas, in addition, the KEGG pathway analysis has shown ...[more]

PMID: 29520253

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Project description:Pediatric adrenocortical carcinomas (ACCs) are aggressive; the overall survival of patients with ACCs is 40%-50%. Appropriate staging and histologic classification are crucial because children with incomplete resections, metastases, or relapsed disease have a dismal prognosis. The clinical course of pediatric adrenocortical tumors (ACTs) is difficult to predict using the current classification schemas, which rely on subjective microscopic and gross macroscopic variables. Recent advances in adult ACT studies have revealed distinct DNA methylation patterns with prognostic significance that have not been systematically interrogated in the pediatric population. We performed DNA methylation analyses on 48 newly diagnosed ACTs from the International Pediatric Adrenocortical Tumor Registry and 12 pediatric adrenal controls to evaluate for distinct methylation groups. Pediatric methylation data were also compared systematically with the adult ACC cohort from The Cancer Genome Atlas (TCGA). Two pediatric ACT methylation groups were identified and showed differences in selected clinicopathologic and outcome characteristics. The A1 group was enriched for CTNNB1 variants and unfavorable outcome. The A2 group was enriched for TP53 germline variants, younger age at onset, and favorable outcome. Pediatric ACT methylation groups were maintained when International Pediatric Adrenocortical Tumor Registry cohort data were combined with TCGA cohort data. The CpG-island hypermethylator phenotype characterizing the TCGA cohort was not identified in the pediatric patients. When methylome findings were combined with independent histopathologic review using the Wieneke criteria, a high-risk population was identified with uniform fatal outcome. Our results indicate DNA methylation analysis can enhance current diagnostic algorithms. A combination of methylation and histologic classification produced the strongest prediction model and may prove useful in future risk-adapted therapeutic trials.

Dataset Information

TCF21/POD-1, a Transcritional Regulator of SF-1/NR5A1, as a Potential Prognosis Marker in Adult and Pediatric Adrenocortical Tumors.

Publications

TCF21/POD-1, a Transcritional Regulator of SF-1/NR5A1, as a Potential Prognosis Marker in Adult and Pediatric Adrenocortical Tumors.

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