Dataset Information

Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma.

ABSTRACT: Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of ATRX and ZNRF3 in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of ATRX and ZNRF3 was associated with a decrease in overall survival (OS) (p = 0.045, p = 0.012, respectively). The Cox regression for ATRX protein expression of >1.5 showed a hazard ratio (HR) for OS of 0.521 (95% CI 0.273-0.997; p = 0.049) when compared with ?1.5; for ZNRF3 expression >2, the HR for OS was 0.441 (95% CI, 0.229-0.852; p = 0.015) when compared with ?2. High ATRX and ZNRF3 protein expressions were associated with optimistic recurrence-free survival (RFS) (p = 0.027 and p = 0.005, respectively). The Cox regression of RFS showed an HR of 0.332 (95%CI, 0.111-0.932) for ATRX expression >2.7 (p = 0.037), and an HR of 0.333 (95%CI, 0.140-0.790) for ZNRF3 expression >2 (p = 0.013). In conclusion, low protein expression of ATRX and ZNRF3 are negative prognostic markers of ACC; however, different cohorts should be evaluated to validate these findings.

SUBMITTER: Brondani VB

PROVIDER: S-EPMC7866180 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma.

Brondani Vania Balderrama VB Lacombe Amanda Meneses Ferreira AMF Mariani Beatriz Marinho de Paula BMP Montenegro Luciana L Soares Iberê Cauduro IC Bezerra-Neto João Evangelista JE Tanno Fabio Yoshiaki FY Srougi Victor V Chambo José Luis JL Mendonca Berenice Bilharinho BB Almeida Madson Q MQ Zerbini Maria Claudia Nogueira MCN Fragoso Maria Candida Barisson Villares MCBV

International journal of molecular sciences 20210127 3

Adrenocortical carcinoma (ACC) is a rare malignancy that is associated with a dismal prognosis. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Our aims were to evaluate the protein expression of ATRX and ZNRF3 in a cohort of 82 adults with ACC and to establish their prognostic value. Two pathologists analyzed immuno-stained slides of a tissue microarray. The low protein expression of ATRX and ZN ...[more]

PMID: 33513905

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Project description:Objective: 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 in silico. Methods: 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. Results: A total of 150 DEGs and 24 significant hub genes with functional enrichment were identified as candidate prognostic biomarkers. LASSO Cox regression suggested that ZWINT, PRC1, CDKN3, CDK1 and CCNA2 were independent prognostic factors in ACC. In multivariate Cox analysis, the integrated expression scores of the modules showed statistical significance in predicting disease-free survival (DFS, P = 0.019) and overall survival (OS, P < 0.001). 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 (P < 0.0001). Conclusion: 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 ZWINT, PRC1, CDKN3, CDK1 and CCNA2 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.

Dataset Information

Low Protein Expression of both ATRX and ZNRF3 as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma.

Publications

Low Protein Expression of both <i>ATRX</i> and <i>ZNRF3</i> as Novel Negative Prognostic Markers of Adult Adrenocortical Carcinoma.

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