Gene Signature Associated With Bromodomain Genes Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma.

Junwan Lu,Changrui Qian,Bin Lu,Qiyu Bao,Yongan Ji

doi:10.3389/fgene.2021.643935

Junwan Lu, Changrui Qian + Show 3 more

Open Access

https://doi.org/10.3389/fgene.2021.643935

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Abstract

Bromodomain (BRD) proteins exhibit a variety of activities, such as histone modification, transcription factor recruitment, chromatin remodeling, and mediator or enhancer complex assembly, that affect transcription initiation and elongation. These proteins also participate in epigenetic regulation. Although specific epigenetic regulation plays an important role in the occurrence and development of cancer, the characteristics of the BRD family in renal clear cell carcinoma (KIRC) have not been determined. In this study, we investigated the expression of BRD family genes in KIRC at the transcriptome level and examined the relationship of the expression of these genes with patient overall survival. mRNA levels of tumor tissues and adjacent tissues were extracted from The Cancer Genome Atlas (TCGA) database. Seven BRD genes (KAT2A, KAT2B, SP140, BRD9, BRPF3, SMARCA2, and EP300) were searched by using LASSO Cox regression and the model with prognostic risk integration. The patients were divided into two groups: high risk and low risk. The combined analysis of these seven BRD genes showed a significant association with the high-risk groups and lower overall survival (OS). This analysis demonstrated that total survival could be predicted well in the low-risk group according to the time-dependent receiver operating characteristic (ROC) curve. The prognosis was determined to be consistent with that obtained using an independent dataset from TCGA. The relevant biological functions were identified using Gene Set Enrichment Analysis (GSEA). In summary, this study provides an optimized survival prediction model and promising data resources for further research investigating the role of the expression of BRD genes in KIRC.

Highlights

The latest database estimates that as incidence rates have doubled in the last several decades, renal carcinoma (RCC) will be the eighth most common tumor in the United States with approximately 70,000 new cases expected in the United States alone and more than 300,000 new cases expected globally by 2020 (Motzer et al, 2017; Bacigalupa and Rathmell, 2020)
The results showed that the 10 genes (SP100, BAZ2B, BAZ1A, BRPF3, SMARCA2, TRIM28, TRIM24, BRD8, BRD7 and BRD2) with higher copy numbers showed higher expression levels
We observed that seven BRD genes (KAT2A, bromodomain-containing protein 9 (BRD9), SP140, EP300, SMARCA2, KAT2B, and BRPF3) can be utilized as new targets for KIRC

Summary

Introduction

The latest database estimates that as incidence rates have doubled in the last several decades, renal carcinoma (RCC) will be the eighth most common tumor in the United States with approximately 70,000 new cases expected in the United States alone and more than 300,000 new cases expected globally by 2020 (Motzer et al, 2017; Bacigalupa and Rathmell, 2020). BRD-containing proteins have a wide range of documented roles in cellular homeostasis These proteins participate in histone modification and regulate the recruitment and segregation of transcriptional machinery components to particular loci in normal tissues (Fujisawa and Filippakopoulos, 2017). BRD-containing proteins are deregulated in cancer cells, and their abnormal expression in various tumors has been shown to both stimulate and inhibit malignant phenotypes These dual roles of certain BRD-containing proteins (such as TRIM24) in tumor promotion and suppression suggest that they have context-dependent functions, which makes their study intriguing (Fujisawa and Filippakopoulos, 2017)

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