AUTHOR=Xu Wen-Hao , Wu Junlong , Wang Jun , Wan Fang-Ning , Wang Hong-Kai , Cao Da-Long , Qu Yuan-Yuan , Zhang Hai-Liang , Ye Ding-Wei 

TITLE=Screening and Identification of Potential Prognostic Biomarkers in Adrenocortical Carcinoma

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.00821

DOI=10.3389/fgene.2019.00821

ISSN=1664-8021

ABSTRACT=<p><bold>Objective:</bold> Adrenocortical carcinoma (ACC) is a rare but aggressive malignant cancer that has been attracting growing attention over recent decades. This study aims to integrate protein interaction networks with gene expression profiles to identify potential biomarkers with prognostic value <italic>in silico</italic>.</p><p><bold>Methods:</bold> Three microarray data sets were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) according to the normalization annotation information. Enrichment analyses were utilized to describe biological functions. A protein–protein interaction network (PPI) of the DEGs was developed, and the modules were analyzed using STRING and Cytoscape. LASSO Cox regression was used to identify independent prognostic factors. The Kaplan–Meier method for the integrated expression score was applied to analyze survival outcomes. A receiver operating characteristic (ROC) curve was constructed with area under curve (AUC) analysis to determine the diagnostic ability of the candidate biomarkers.</p><p><bold>Results:</bold> A total of 150 DEGs and 24 significant hub genes with functional enrichment were identified as candidate prognostic biomarkers. LASSO Cox regression suggested that <italic>ZWINT</italic>, <italic>PRC1</italic>, <italic>CDKN3</italic>, <italic>CDK1</italic> and <italic>CCNA2</italic> were independent prognostic factors in ACC. In multivariate Cox analysis, the integrated expression scores of the modules showed statistical significance in predicting <bold>disease-free survival (DFS, <italic>P</italic> =  0.019) and overall survival (OS, <italic>P</italic> &lt; 0.001)</bold>. Meanwhile, ROC curves were generated to validate the ability of the Cox model to predict prognosis. The AUC index for the integrated genes scores was 0.861 (<italic>P</italic> &lt; 0.0001).</p><p><bold>Conclusion:</bold> In conclusion, the present study identifies DEGs and hub genes that may be involved in poor prognosis and early recurrence of ACC. The expression levels of <italic>ZWINT</italic>, <italic>PRC1</italic>, <italic>CDKN3</italic>, <italic>CDK1</italic> and <italic>CCNA2</italic> are of high prognostic value, and may help us understand better the underlying carcinogenesis or progression of ACC. Further studies are required to elucidate molecular pathogenesis and alteration in signaling pathways for these genes in ACC.</p>