Abstract 3422: Alteration of aldo-keto reductase family 1, member B10 (AKR1B10) expression among tumor and background non-tumorous tissue of curatively resected hepatocellular carcinoma is associated with worse prognosis

Abstract

Abstract Background and Objectives: When assessing hepatocellular carcinoma (HCC), it is quite important to examine prognostic factors in the background non tumorous liver tissue as well as HCC tissue itself. We tried to elucidate molecular prognostic predictors which have some relation with both tumor and background tissue for curatively resected HCC. Methods: Candidate genes were extracted from the background non tumorous liver samples via microarray analysis. Control samples, termed super normal (SN) liver, were obtained from 11 cases of metastatic liver cancer. Corresponding non tumorous liver tissue (CN) was surgically obtained from a typical HCC patient with chronic hepatitis C background for comparison. Expression profiling microarray demonstrated 4 genes as candidates for prognostic factors. Among them, Aldo-keto reductase family 1, member B10 (AKR1B10) was extracted to investigate in 158 consecutive curatively resected HCC cases by real-time quantitative reverse transcription polymerase chain reaction. The relation between AKR1B10 expression and clinicopathological factors were assessed and statistical analyses were performed with Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional hazards models were used to determine the independent risk factors associated with the RFS and OS. Results: The expression level of AKR1B10 (expression score/GAPDH×1000) was significantly higher in HCC tissues (median: 9.22 [range: 0.0003-611.02], n = 158) than in CN (0.5461[0.0018-69.03], n = 158) tissues (P < 0.001). 158 HCC cases were subsequently divided into two groups based on AKR1B10 expression in tumor and CN in each case: one consisting of the T ≥ CN cases (n = 132) and the other of the T < CN (n = 26). T < CN cases demonstrated significant correlation with worse recurrence-free survival (P = 0.0074) and overall survival (P<0.0001). Furthermore, multivariate analysis identified AKR1B10 expression T<CN as an independent prognostic factor in overall survival (P = 0.0011). The alteration of AKR1B10 expression level in T and CN was significantly correlated between liver damage score (B or C / A) (P = 0.035) and infiltration to capsule (+ / -) (P = 0.0284) respectively. Conclusions: Our findings suggested that basically, AKR1B10 expression is much higher in T than in CN but once AKR1B10 expression inversion between tumor and CN occurs; its prognosis becomes significantly worse. This T<CN change may well expressed both CN ill status and T malignancy. This alteration might be one of the good and suggestive prognostic predictors for resected HCC. Citation Format: Shuji Nomoto, Fuminori Sonohara, Yoshikuni Inokawa, Mitsuro Kanda, Tsutomu Fujii, Hiroyuki Sugimoto, Masahiko Koike, Michitaka Fujiwara, Yasuhiro Kodera. Alteration of aldo-keto reductase family 1, member B10 (AKR1B10) expression among tumor and background non-tumorous tissue of curatively resected hepatocellular carcinoma is associated with worse prognosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3422. doi:10.1158/1538-7445.AM2015-3422