Prognostic Value of Long Non-Coding RNA HULC and MALAT1 Following the Curative Resection of Hepatocellular Carcinoma

Fuminori Sonohara,Shuji Nomoto,Tsutomu Fujii,Yoshikuni Inokawa,Suguru Yamada,Yasuhiro Kodera,Masamichi Hayashi,Hiroyuki Sugimoto

doi:10.1038/s41598-017-16260-1

Fuminori Sonohara, Shuji Nomoto + Show 6 more

Open Access

https://doi.org/10.1038/s41598-017-16260-1

Copy DOI

Journal: Scientific Reports	Publication Date: Nov 23, 2017
Citations: 23	License type: open-access

Affiliation: Nagoya University, Aichi Gakuin University

Abstract

Long non-coding RNAs (lncRNAs) were shown to be the crucial regulators of the many diseases. In this study, the expressions of lncRNAs were investigated in resected 158 hepatocellular carcinomas (HCCs) to evaluate the effects of their expression levels on prognosis. The expression levels of HULC and MALAT1 were shown to be significantly higher in the normal background tissue of HCC than those in the normal liver tissue of metastatic liver tumor without hepatitis (HULC: fold change 14.9, P = 1.7e-06; MALAT1: fold change 17.5, P = 1.2e-06. The formation of capsule was shown to be correlated with the increased expression of HULC (P = 0.041), while the size of HCC under 2 cm was correlated with a decrease in MALAT1 expression (P = 0.019). The levels of serum alpha-fetoprotein above 20 ng/mL indicated a decreased expression of both HULC and MALAT1 (HULC: P = 0.017; MALAT1: P = 0.0036). The increase in the expression levels of MALAT1 in HCC tissues was significantly correlated with better overall survival (HULC: P = 0.099, MALAT1: P = 0.028). Thus, the expression of these lncRNAs in HCC potentially correlates with the HCC malignancy and they represent potential prognostic biomarkers of the resected HCC.

Highlights

Long non-coding RNAs were identified as the key players in tumorigenesis and tumor progression
Microarray analysis revealed that Long non-coding RNAs (lncRNAs) upregulated in the CN sample were Urothelial Cancer Associated 1 (UCA1: fold change 7.98), HULC, MALAT1, Growth Arrest Specific 5 (GAS5: fold change 1.28), and Taurine Up-Regulated 1 (TUG1: fold change 1.27) (Supplementary Table S1)
With the development of whole genome and transcriptome sequencing, many lncRNAs were shown to be highly expressed in tumor tissue19

Summary

Introduction

Long non-coding RNAs (lncRNAs) were identified as the key players in tumorigenesis and tumor progression. Many reports showed that lncRNA dysregulation is linked to the development of many diseases, including cancer. We hypothesized that the expression of lncRNAs in the background liver tissue of HCC may be important for HCC prognosis as well. We attempted to identify novel lncRNAs related to HCC prognosis by using the microarray analysis of their expression in the background liver tissue of HCC patients and normal liver tissue without HCC and/or hepatitis. We evaluated the differences in lncRNA expression levels in HCC and corresponding non-tumor tissues, and identified the unique prognostic markers for the HCC

Methods

Results

Conclusion