[Background & Aim] Hepatocellular carcinoma (HCC) often recurs in the liver after surgery removing the primary lesion. Multi-centric occurrence (MO) is more common than intrahepatic metastases (IM). Then, it is insufficient to predict the prognosis by considering factors only 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. We selected a corresponding non-neoplastic (CN) tissue of a typical HCC case with chronic hepatitis C as a sample to compare. Then, expression profiling and methylation arrays were performed for comparing the SN and the CN. We identified genes showing differences in gene expression and the rate of methylation. Prognosis was predicted for 100 cases of HCC based on gene expression.

[Results] The expression profiling showed that expression of Janus kinase 2 (JAK2) gene was increased 2.378 in CN, and methylation array analysis showed a lower value for CN (0.13) than SN (0.75). We then studied JAK2 gene expression by quantitative real time RT-PCR. Unfortunately, the average expression value of JAK2 (JAK2 x103/GAPDH) had decreased in matching normal tissue (9.24±7.46) relative to SN (35.21±21.38). Only one case was expressed higher than SN average in CN. We divided the cases into two groups. Group A showed higher 70% of JAK2 expression cases (70 cases) and group B showed lower 30% of expression cases (30 cases). Then, the group A had a significant correlations with worth prognosis (p=0.017) by univariate analysis and showed independent worth prognostic factor (p = 0.032) by multivariate analysis.

[Discussion & Conclusion] It has been reported that JAK2 has an important role in reproduction of normal hepatocyte, and maintenance of liver functions in the super normal liver. While, in HCC tissues, STAT3-JAK2 pathway was reported as an oncogenic factor in proliferation and progression. In this study, the expression of the JAK2 gene in the background liver in HCC cases also had an important meaning and likely to be a good biomarker. When assessing cases of HCC, as well as considering malignant factor of the primary cancer lesion, it is important to extract prognostic factors from background liver tissue.

Citation Format: Shuji Nomoto, Mitsuhiro Hishida, Yoshikuni Inokawa, Nao Takano, Mitsuro Kanda, Yasuhiro Kodera. Correlation between worse prognosis and higher expression of the JAK2 gene in corresponding non-neoplastic tissue in patients with hepatocellular carcinoma, extracted by multiarray analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3816. doi:10.1158/1538-7445.AM2014-3816