Abstract 3539: A study of THOP1, a predictive factor of prognosis in HCC, by multi-array analysis of background liver.
Authors: Nomoto Shuji , Hishida Mitsuhiro , Inokawa Yoshikuni , Kanda Mitsuro , Sugimoto Hiroyuki , Fujii Tsutomu , Kodera Yasuhiro 
Published: August 2014

Background & Aim Hepatocellular carcinoma (HCC) often recurs in the liver after surgery removing the primary lesion. Multi-centric occurrence is more common than intrahepatic metastases.We have previously reported it by showing genotype of recurrent HCC, either by detecting the alteration of mitochondrial mutations (NomotoS et al. Clin Cancer Res. 2002 8:481-7), or by examining patterns of promoter hypermethylation in several tumor suppressor genes (Nomoto S. et al. Br J Cancer. 2007 97:1260-5) in tumor cell. Therefore, it is insufficient to predict prognosis by only considering factors in resected primary tumor. Factors in the background liver will also play important roles in prognosis.

Material & Methods Our control samples, termed super normal (SN) liver, were taken from normal tissues of 11 cases of metastatic liver cancer that underwent liver resection at our department. We selected a corresponding normal tissue of a typical case in which HCC was generated from chronic hepatitis C (CN) as a sample to compare. DNA and RNA were extracted from the cases. To eliminate the personal background, the DNA and RNA of 11 SN cases were mixed. Then, expression profiling and methylation arrays were performed to compare the SN and the CN. We identified genes showing differences in both expression and the rate of methylation. Prognosis was predicted for 48 cases of HCC based on gene expression.

Results & Discussion The expression profiling showed that expression of the THOP1 gene was decreased -4.119 in CN, and methylation array analysis showed a higher value for CN (0.86) than SN (0.48). We then studied THOP1 gene expression by quantitative real time RT (Reverse Transcription)-PCR. The average expression value of THP1 (THOP1 x103/GAPDH) had decreased in matching normal tissue (22.17) relative to SN (78.14). We divided the 48 cases into two groups, where Group A showed higher THOP1 expression than the average value (16 cases) and group B showed lower expression than average (32 cases). Group A correlated significantly with a highly differentiated histological type (p=0.0228) and a tendency to associate with a lack of vascular invasion (p=0.057). In addition, Group A showed significant correlations with prolonged survival (p = 0.0045) and recurrence-free survival (p = 0.001). This suggests that the expression of the THOP1 gene in the background liver of HCC cases is likely to be a good biomarker to predict survival and recurrence of HCC.

Conclusion When assessing cases of HCC, as well as considering malignant factors of the primary cancer lesion, it is important to extract prognostic factors from the background liver tissue.

Citation Format: Shuji Nomoto, Mitsuhiro Hishida, Yoshikuni Inokawa, Mitsuro Kanda, Hiroyuki Sugimoto, Tsutomu Fujii, Yasuhiro Kodera. A study of THOP1, a predictive factor of prognosis in HCC, by multi-array analysis of background liver. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3539. doi:10.1158/1538-7445.AM2013-3539