Abstract 3822: Correlation between worse prognosis and lower expression of the TPPP gene in patients with hepatocellular carcinoma, detected by multiarray analysis

Abstract

Abstract Background. Hepatocellular carcinoma (HCC) patients who undergo liver resection often suffer multicentric occurrence after surgery. Therefore, understanding carcinogenesis in background liver is important. Methods. Control liver samples (super normal [SN]), were taken from 11 cases of metastatic liver cancer. We selected corresponding normal tissue from typical cases of HCC with chronic hepatitis C (corresponding normal [CN]) for comparison. Expression profiling and methylation arrays were performed to compare SN and CN. Array data showed that the tubulin polymerization promoting protein (TPPP) gene showed differences in both array analyses. The relationship between clinicopathological factors of 179 HCC patients and TPPP expression was investigated. Results. The expression array showed that the TPPP gene was decreased by 2.236-fold (log2 ratio) in CN compared with SN. The methylation array showed a higher value of methylation for CN (0.730) than SN (0.384). We studied TPPP gene expression by real-time reverse transcription PCR. When compared expression level of TPPP (TPPP value ×103/GAPDH), among SN (n=11), normal liver tissue of HCC patients (n=179), and tumor tissue of HCC (n=179), there were significant differences (median: 116, 4.60, and 2.63, respectively). The group with lower TPPP expression in tumors compared with normal tissue showed a worse prognosis of overall survival than that in the increased expression group (P=0.0317). Strongly reduced TPPP expression in tumor tissue compared with normal tissue (ratio <0.3, n=57) was detected as an independent prognostic factor by multivariate analysis (P=0.0310). Conclusions. Expression of the TPPP gene in tumor and non-cancerous liver tissue in HCC patients is significantly lower compared with SN. HCC patients with this low TPPP expression show a poor prognosis. This indicates that this gene is a new candidate of tumor suppressor genes in HCC. Low TPPP expression in liver tissue might be a predictor of HCC. Citation Format: Yoshikuni Inokawa, Shuji Nomoto, Mitsuhiro Hishida, Nao Takano, Mitsuro Kanda, Michitaka Fujiwara, Masahiko Koike, Hiroyuki Sugimoto, Tsutomu Fujii, Goro Nakayama, Suguru Yamada, Chie Tanaka, Daisuke Kobayashi, Naoki Iwata, Yasuhiro Kodera. Correlation between worse prognosis and lower expression of the TPPP gene in patients with hepatocellular carcinoma, detected 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 3822. doi:10.1158/1538-7445.AM2014-3822