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Page 2 of 7 Tian et al. Hepatoma Res 2018;4:27 I http://dx.doi.org/10.20517/2394-5079.2018.24

Keywords: Plasmacytoma variant translocation 1, expression quantitative trait loci, long non-coding RNA,
hepatocellular carcinoma, survival

INTRODUCTION
Liver cancer is the second most common cause of cancer death in the world, of which hepatocellular
[1]
carcinoma (HCC) is the predominant form . Ranked as the sixth most common form of cancer, HCC
[2]
is also the third leading cause of cancer death . In previous study, 3-year survival rate among patients
[3]
at intermediate stages was 50%, whereas among those at advanced stage was just 8% . Although several
therapies including radiofrequency ablation, liver transplantation, tumor resection and some others are the
[4,5]
potentially effective treatments for HCC, HCC still has a poor 5-year survival rate of about 7% . Due to
different factors of disease and the poor survival outcomes of HCC patients, it is crucial to identify beneficial
molecular biomarker to guide individualized treatment and to improve the prognosis of cancer patients.

[6]
Non-coding RNAs (ncRNAs) are emerging as novel regulatory factor in the cancer paradigm . Long
noncoding RNAs (lncRNAs), longer than 200 nucleotides in length, are evolutionarily conserved non-
[7]
protein coding RNAs . LncRNAs have been reported to play an important role in various biological
processes related to cancer progressions, such as proliferation, apoptosis and invasion. Plasmacytoma
[7]
variant translocation 1 (PVT1), a long intergenic non-coding RNA, is located in the chr8q24.21 region .
[8]
Chromosome 8q24 contains a locus conferring an increased risk for multiple cancers . Recently, several
studies have found that PVT1 was functioned as an oncogene and was overexpressed in human tumors
[9]
including cervical cancer, serous melanoma and prostate cancer . In addition, it was also reported that
[9]
PVT1 overexpression was associated with clinicopathological features and reduced patients’ survival times .
However, the potential function of PVT1 expression quantitative trait loci (eQTL) in the prognosis of HCC
has been rarely discussed.

In this study, we identified one single nucleotide polymorphism (SNP) (rs4733586) that may be the eQTL
for PVT1 (http://www.regulomedb.org) by using the bioinformatics analysis. Therefore, we thought that the
SNP rs4733586 may be likely to regulate the expression of PVT1. Here, we assumed that PVT1 eQTL may
contribute to the development and progression of HCC. To verify our hypothesis, we examined the effect of
the PVT1 eQTL (rs4733586) on the HCC prognosis of 331 patients from Han population.

METHODS
Study subjects
This study was authorized by the local institutional review board at Nanjing Medical University. After
approval by the ethics committees, all the participants were given written informed consent, and the
registration of the participants was described before [10,11] . In brief, all the patients were consecutively
recruited from Nantong Tumor Hospital and the First Affiliated Hospital of Nanjing Medical University,
[12]
Jiangsu, China , and were face-to-face interviewed to collect the demographic information including age,
gender, smoking and drinking status. We recruited patients with HCC with hepatitis B virus (HBV) and
excluded those with hepatitis C virus (HCV). All the subjects were diagnosed as HCC by histopathological
examination. To construct a relatively homogeneous population, our study was limited to HCC patients
who have not undergone surgery in intermediate stage (B) or advanced stage (C) according to the Barcelona
[13]
Clinic Liver Cancer (BCLC) staging system . Eventually, 331 of 414 intermediate or advanced HCC patients
completed the follow-ups with the response rate of 80.0% and were performed the survival analysis. We
followed up the study subjects every 3 months from the time of recruitment until the death or the last time
of follow-up (January 2013).