Abstract

BackgroundAdrenocortical adenomas (ACAs) can lead to the autonomous secretion of aldosterone responsible for primary aldosteronism (PA), which is the most common form of secondary arterial hypertension. However, the authentic fundamental mechanisms underlying ACAs remain unclear.ObjectiveIsobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics and bioinformatics analyses from etiological studies of ACAs were performed to screen the differentially expressed proteins (DEPs) and investigate the relevant mechanisms of their occurrence and development. Results could help determine therapeutic targets of clinical significance.MethodsIn the present study, iTRAQ-based proteomics was applied to analyze ACA tissue samples from normal adrenal cortex tissues adjacent to the tumor. Using proteins extracted from a panel of four pairs of ACA samples, we identified some upregulated proteins and other downregulated proteins in all four pairs of ACA samples compared with adjacent normal tissue. Subsequently, we predicted protein–protein interaction networks of three DEPs to determine the authentic functional factors in ACA.ResultsA total of 753 DEPs were identified, including 347 upregulated and 406 downregulated proteins. The expression of three upregulated proteins (E2F3, KRT6A, and ALDH1A2) was validated by Western blot in 24 ACA samples. Our data suggested that some DEPs might be important hallmarks during the development of ACA.ConclusionsThis study is the first proteomic research to investigate alterations in protein levels and affected pathways in ACA using the iTRAQ technique. Thus, this study not only provides a comprehensive dataset on overall protein changes but also sheds light on its potential molecular mechanism in human ACAs.

Highlights

  • Adrenocortical adenomas (ACAs) can lead to the autonomous secretion of aldosterone responsible for primary aldosteronism (PA), which is the most common form of secondary arterial hypertension

  • The proportion of each classification can reflect the impact of biological factors on each classification in the experimental design to a certain extent, evaluations on the significance of each classification depending on the ratio alone are inaccurate

  • The isobaric tags for relative and absolute quantitation (iTRAQ) technique is a powerful tool for the identification of protein isoforms and comparative proteome studies

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Summary

Introduction

Adrenocortical adenomas (ACAs) can lead to the autonomous secretion of aldosterone responsible for primary aldosteronism (PA), which is the most common form of secondary arterial hypertension. Adrenocortical adenomas (ACAs) can lead to the autonomous secretion of aldosterone responsible for PA [3], which is the most frequent form of secondary arterial hypertension [4, 5]. Ma et al BMC Genomics (2019) 20:655 research on the mechanisms of ACA Both isobaric tags for relative and absolute quantitation (iTRAQ) and label-free methods have been broadly applied for quantitative proteomics [13,14,15,16]. Establishing differentially expressed protein–protein interaction (PPI) networks using bioinformatic data will lead to an improved understanding of the pathogenesis of ACA

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