Identification of The Aberrantly Expressed LncRNAs in Hepatocellular Carcinoma: A Bioinformatics Analysis Based on RNA-sequencing

Hao-Tian Liao,Ke-Fei Yuan,Tian Lan,Jin-Ju Wang,Yong Zeng,Bo Zhu,Ji-Wei Huang

doi:10.1038/s41598-018-23647-1

Hao-Tian Liao, Ke-Fei Yuan + Show 5 more

Open Access

https://doi.org/10.1038/s41598-018-23647-1

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Journal: Scientific Reports	Publication Date: Mar 29, 2018
Citations: 28	License type: open-access

Affiliation: Sichuan University

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent subtypes of liver cancer worldwide. LncRNAs have been demonstrated to be associated with the progression of HCC, but a systematic identification and characterization of their clinical roles and molecular mechanisms in HCC has not been conducted. In this study, the aberrantly expressed lncRNAs in HCC tissues were analyzed based on TCGA RNA-seq data. 1162 lncRNAs were found to be aberrantly expressed in HCC tissues, including 232 down-regulated lncRNAs and 930 up-regulated lncRNAs. The top 5 lncRNAs with the highest diagnostic accuracy were further analyzed to evaluate their clinical value and potential mechanism in HCC. Kaplan-Meier curves showed that higher expressions of DDX11-AS1 and AC092171.4 were in correlation with poorer survival in HCC patients. Significant difference was also observed when comparing the expression levels of DDX11-AS1 and SFTA1P in different clinical parameters (p < 0.05). GO analysis showed that genes regulated by the 5 lncRNAs were enriched in certain pathways, such as PI3K pathway. Moreover, GSEA analysis on the expression of DDX11-AS1 showed that DDX11-AS1 affected the gene expressions involved in HCC proliferation, differentiation and cell cycle, indicating an essential role of DDX11-AS1 in hepatocarcinogenesis.

Highlights

In this study, we performed bioinformatical analyses based on high throughput RNA sequencing of Hepatocellular carcinoma (HCC) from The Cancer Genome Atlas database (TCGA, http://cancergenome.nih.gov/) to evaluate the clinicopathological value of lncRNAs and their underlying mechanism in HCC
1162 lncRNAs were found to be aberrantly expressed in HCC tissues, including 232 down-regulated lncRNAs and 930 up-regulated lncRNAs (Fig. 1). 5 lncRNAs with area under ROC curve (AUC) over 0.95 were selected for further analysis due to their potential roles in hepatocarcinogenesis and significant diagnostic value for patients with HCC, including HOXD antisense growth-associated long non-coding RNA (HAGLR), HAGLR opposite strand (HAGLROS), Surfactant associated 1 (SFTA1P), DDX11 antisense RNA 1 (DDX11-AS1) and AC092171.4 (Fig. 2)
Kaplan-Meier curves showed that higher expressions of DDX11-AS1 and AC092171.4 were in correlation with poorer survival in HCC patients (p = 0.0001 and 0.0411, respectively), while the expressions of HAGLR, HAGLROS and SFTA1P were not associated with the HCC-specific survival (Fig. 5)

Summary

Introduction

We performed bioinformatical analyses based on high throughput RNA sequencing of HCC from The Cancer Genome Atlas database (TCGA, http://cancergenome.nih.gov/) to evaluate the clinicopathological value of lncRNAs and their underlying mechanism in HCC. The differentially expressed lncRNAs between HCC samples and paired adjacent normal tissues were determined by using the statistical methods of DESeq, in which genes with Benjamini-Hochberg adjusted p value < 0.05 and absolute log[2] fold-change >2 were considered differentially expressed.

Results

Conclusion