Abstract 1493: Lysyl oxidase expression is associated with early recurrence and poor survival in hepatocellular carcinoma
Authors: Umezaki Naoki , Nakagawa Shigeki , Yamao Takanobu , Tsukamoto Masayo , Arima Kota , Miyata Tatsunori , Okabe Hirohisa , Imai Katsunori , Yamashita Yo-ichi , Nitta Hidetoshi , Chikamoto Akira , Baba Hideo 
Published: August 2018

Abstract
Background: Hepatectomy is one of the an established one of a curative treatment for hepatocellular carcinoma (HCC). However, HCC has is a disease that high recurrence rates even after curative hepatectomy. We searched the gene for the prediction of the HCC recurrence from intrahepatic metastasis.
Methods: For the gene selection, we used public data base (GSE10141) and searched genes with hHigh early recurrence rate and higher expression genes in tumor area compared with background liver. We detected Lysyl oxidase. As a validation cohort, From 2004 to 2012, 149 patients underwent hepatectomy at Kumamoto University Hospital from 2004 to 2012 were enrolled. The expression of target gene was evaluated by real time PCR. Upper 25% patients were considered as the high expression group, and the other 75% patients were considered as the low expression group. The immunehistochemical (IHC) staining was evaluated with the intensity and area of immunoreactivity of LOX and were scored each factors from 0 to 3. Low expression of LOX group was for scores from 0 to 5. The ones with scores from 6 to 9 were defined as high expression of LOX.
Result: As a first step toward discovering the targets genes, we investigated using GSE 10141, which is a microarray database of cancerous part and background liver tissue of hepatocellular carcinoma cases to select genes useful as drug therapy targets. We extracted LOX as a genes with high hazard ratio (HR &gt; 3) forof early recurrence to select genes useful as prevention of early recurrence. In real time PCR, LOX high expression group had a significantly high recurrence rate (2 years recurrence rate was 64.3% VS 42.7%, p = 0.024) and poor survival rate (3 years rate was 62.7% VS 82.0%, p = 0.0441) than LOX low expression group. Moreover, in the comparisons of clinicopathological factors between LOX high and low expression, there was significantly more Vp positive patients in the LOX high expression group (p = 0.004). Multivariate Analysis demonstrated that Tumor size larger than 50 mm (HR, 2.20; p = 0.002), LOX high expression (HR, 1.73; p = 0.04) were independent risk factors for early recurrence. In immunohistochemistry, LOX high expression group had a significantly high recurrence rate (2 years recurrence rate was 58.5% VS 42.3%, p = 0.004) and poor survival rate (3 years rate was 65.1% VS 88.8%, p = 0.004) than LOX low expression. In addition the comparisons of clinicopathological factors between LOX high and low expression, there was significantly more Ig positive patients in the LOX high expression group (p = 0.04). Multivariate Analysis demonstrated that PIVKA-II score higher than 100 (HR, 1.84; p = 0.03), multiple tumors tumor more than 2 pieces (HR, 2.11; p = 0.009), LOX high expression (HR, 1.90; p = 0.014) were independent risk factors for early recurrence.
Conclusion: LOX high expression is associated with early recurrence and poor survival in HCC.
Citation Format: Naoki Umezaki, Shigeki Nakagawa, Takanobu Yamao, Masayo Tsukamoto, Kota Arima, Tatsunori Miyata, Hirohisa Okabe, Katsunori Imai, Yo-ichi Yamashita, Hidetoshi Nitta, Akira Chikamoto, Hideo Baba. Lysyl oxidase expression is associated with early recurrence and poor survival in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1493.