TBX5-AS1, an enhancer RNA, is a potential novel prognostic biomarker for lung adenocarcinoma

Lin Cheng,Bolin Chen,Kechao Nie,Weijun Peng,Tong Han

doi:10.1186/s12885-021-08517-w

Abstract

BackgroundEnhancer RNAs (eRNAs) are demonstrated to be closely associated with tumourigenesis and cancer progression. However, the role of eRNAs in lung adenocarcinoma (LUAD) remains largely unclear. Thus, a comprehensive analysis was constructed to identify the key eRNAs, and to explore the clinical utility of the identified eRNAs in LUAD.MethodsFirst, LUAD expression profile data from the Cancer Genome Atlas (TCGA) dataset and eRNA-relevant information were integrated for Kaplan-Meier survival analysis and Spearman’s correlation analysis to filtered the key candidate eRNAs that was associated with survival rate and their target genes in LUAD. Then, the key eRNA was selected for subsequent clinical correlation analysis. KEGG pathway enrichment analyses were undertaken to explore the potential signaling pathways of the key eRNA. Data from the human protein atlas (HPA) database were used to validate the outcomes and the quantitative real time-polymerase chain reaction (qRT-PCR) analysis was conducted to measure eRNA expression levels in tumor tissues and paired normal adjacent tissues from LUAD patients. Finally, the eRNAs were validated in pan-cancer.ResultsAs a result, TBX5-AS1 was identified as the key eRNA, which has T-box transcription factor 5 (TBX5) as its regulatory target. KEGG analysis indicated that TBX5-AS1 may exert a vital role via the PI3K/AKT pathway, Ras signaling pathway, etc. Additionally, the qRT-PCR results and the HPA database indicated that TBX5-AS1 and TBX5 were significantly downregulated in tumour samples compared to matched-adjacent pairs. The pan-cancer validation results showed that TBX5-AS1 was associated with survival in four tumors, namely, adrenocortical carcinoma (ACC), LUAD, lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). Correlations were found between TBX5-AS1 and its target gene, TBX5, in 26 tumor types.ConclusionCollectively, our results indicated that TBX5-AS1 may be a potential prognostic biomarker for LUAD patients and promote the targeted therapy of LUAD.

Highlights

Enhancer RNAs are demonstrated to be closely associated with tumourigenesis and cancer progression
Screening the key Enhancer RNAs (eRNAs) in lung adenocarcinoma (LUAD) Using the Kaplan-Meier method, eRNAs with P-values adjusted according to the false discovery rate (FDR) cut-off of < 0.05 were extracted as survival-related eRNAs in LUAD
Spearman’s correlation was used to screen these 174 eRNAs to identify those with a significant correlation with their target genes that were associated with LUAD

Summary

Introduction

Enhancer RNAs (eRNAs) are demonstrated to be closely associated with tumourigenesis and cancer progression. In T-cell acute lymphoblastic leukemia (T-ALL), it was reported that the eRNA ARIEL could recruit mediator proteins to the ARID5B enhancer, thereby boosting enhancer-promoter interactions and activating the expression of ARID5B. These activities led to the aberrant activation of the TAL1-induced transcriptional program and myc oncogenic signals [21]. Related research has demonstrated that the NET1-associated eRNA (NET1e) could upregulate the expression of its target gene and promote breast cancer progression. To date, no study has investigated the potential of using eRNAs as biomarkers to predict the survival of patients with LUAD

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Discussion

Conclusion