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.
Highlights
The molecular pathogenesis of adrenocortical tumors (ACTs) remains poorly understood despite recent advances provided by comprehensive clinical and molecular investigations [1, 2]
The relative expression levels of Transcription factor 21 (TCF21), budding uninhibited by benzimidazoles 1 homolog beta (BUB1B), PTEN-induced putative kinase 1 (PINK1), and NR5A1 were similar in childhood ACTs, regardless of the group studied (Figures 2 and 3)
To test whether the induction of TCF21 expression affected BUB1B or PINK1 expression in the NCI-H295R adrenocortical carcinomas (ACCs) cell line, we performed RT-qPCR of BUB1B or PINK1 in cells transiently transfected with the expression vector pCMVMycPOD1
Summary
The molecular pathogenesis of adrenocortical tumors (ACTs) remains poorly understood despite recent advances provided by comprehensive clinical and molecular investigations [1, 2]. Among these studies, a microarray analysis [4] showed that 91 genes are differentially expressed between adrenocortical carcinomas (ACCs) and adrenocortical adenomas (ACAs) of adult patients, including the TCF21 gene, which was two times lower in ACCs than in ACAs or in normal adrenal cortex samples. TCF21 directly regulates the expression of steroidogenic factor 1 (NR5A1/SF1) in human ACT cells by binding to the E-box sequence in the NR5A1’s promoter region [10]. In this study, we showed that the viability of ACC cells transfected with TCF21 was not affected. KEGG analysis showed a significant enrichment in cell cycle regulation pathways involving genes whose expression was negatively correlated with TCF21 expression in ACCs, such as CDK1 and BUB1B [10]. ΔCTBUB1B − ΔCTPINK1 was considered a prognostic factor in ACCs in two different cohorts [14, 15]
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