Abstract 2870: ZGPAT gene expression in non-tumor hepatocellular carcinoma tissue is a likely biomarker for survival risk

Abstract

Abstract [Background & Aim] Hepatocellular carcinoma (HCC) often recurs after surgery and multicentric occurrence is more common than intrahepatic metastasis. We therefore examined factors in non-tumor liver tissue in HCC. [Material & Methods] Control samples, termed super normal liver tissues (SN), were taken from 11 cases of metastatic liver cancer. One of corresponding samples of normal tissues (CN) was selected for comparison from a typical specimen with chronic hepatitis C and HCC. We performed expression profiling and methylation arrays on these samples, identified genes that differed between SN and CN. We analyzed the identified genes using quantitative real-time reverse-transcriptase polymerase chain reaction on SN from 11 cases of metastatic liver cancer and CN from 109 cases of HCC. [Results] We found the zinc finger, CCCH-type with G patch domain (ZGPAT) gene to have expression decreased 4.198-fold in CN, and higher methylation status in CN (0.718), than in SN (0.360). The average expression value of the ZGPAT gene (ZGPAT value ×103 / GAPDH) decreased in CN (9.94 ± 10.68) relative to SN (28.55 ± 22.05). Compared with other patients, those with strongly reduced ZGPAT expression (< 1.5) in their non-tumor liver samples had significantly shorter overall survival (P = 0.024), but not recurrence-free survival (P = 0.515). [Discussion & Conclusion] Our results indicate that expression of the ZGPAT gene in non-tumor liver tissue is a good biomarker for the risk of HCC development. ZGPAT gene is reportedly a transcription repressor that negatively regulates expression of epidermal growth factor receptor, which in turn, mediates cell proliferation, survival, migration. In treating HCC, detection of both prognostic factors from non-tumor liver tissue and malignant factors of the primary cancer lesion is important. Citation Format: Mitsuhiro Hishida, Shuji Nomoto, Yoshikuni Inokawa, Nao Takano, Mitsuro Kanda, Naoki Iwata, Chie Tanaka, Daisuke Kobayashi, Yoko Nishikawa, Suguru Yamada, Goro Nakayama, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera. ZGPAT gene expression in non-tumor hepatocellular carcinoma tissue is a likely biomarker for survival risk. [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 2870. doi:10.1158/1538-7445.AM2014-2870