Plasma HULC as a promising novel biomarker for the detection of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer death in many Asian and African countries. Lack of early diagnosis tools is one of the clinical obstacles for effective treatment of HCC. Thus, enhanced understanding of the molecular changes associated with HCC is urgently needed to develop novel strategies for the diagnosis and treatment of this dismal disease. While aberrant expression of long noncoding RNAs (lncRNAs) has been functionally associated with certain cancers, the expression profiles and biological relevance of lncRNAs in HCC remain unclear. Highly upregulated in liver cancer (HULC) lncRNA has been implicated in the regulation of hepatoma cell proliferation. In this study, we demonstrate that HULC expression is significantly higher in HCC tumors compared to normal liver tissues. Among the tumor tissues, higher HULC expression is positively associated with Edmondson histological grades or with hepatitis B (HBV) positive status. Moreover, HULC lncRNA is detected with higher frequency in the plasma of HCC patients compared to healthy controls. Higher HULC detection rates are observed in the plasma of patients with higher Edmondson grades or with HBV+ status. These findings indicate for the first time that the expression of HULC in plasma can be used as a noninvasive promising novel biomarker for the diagnosis and/or prognosis of HCC.

Figure 1

HULC is up-regulated in HCC tissues. Receiver-operating characteristic (ROC) curve (a) and box plots (b) of HULC RNA expression in HCC tissues and healthy control liver tissues. (a) The area under the ROC curve was 0.86 in distinguishing hepatocellular carcinoma versus healthy control. (b) HULC expression was examined in 20 healthy control liver tissues and 30 HCC tissues by qRT-PCR. Data were analyzed using the 2^−ΔΔCt method. The upper and lower limits of the boxes and the lines inside the boxes indicate the 75th and 25th percentiles and the median, respectively. The upper and lower horizontal bars denote the 90th and 10th percentiles, respectively.

Figure 2

HULC lncRNA expression is associated with HCC Edmondson grades and HBV status. (a) Comparison of the relative levels of HULC in normal liver tissues and HCC tissues with different Edmondson grades. (b) Comparison of the relative levels of HULC in normal liver tissues and HCC tissues from HBV− and HBV+ patients.