Abstract 2146: High expression of Olfactomedin-4 correlates with chemoresistance and poor prognosis for pancreatic cancer

Abstract

Abstract Background: Pancreatic cancer has an extremely poor prognosis and novel therapeutic strategies are desperately needed. It is considered that suitable molecules as therapeutic targets are resistant to chemotherapy and correlate with poor prognosis. In this experiment, we aimed to identify the optimal therapeutic targets in pancreatic cancer. Materials and Methods: We established 10 lines of patient derived xenografts (PDXs) for pancreatic cancer. Next generation sequencer (NGS) analysis was performed for PDXs which were administered chemotherapy and untreated PDXs as a control. Furthermore, we performed immunohistochemistry (IHC) analysis for the protein expression of identified molecules from PDXs and post-operative pathologic specimens from 80 patients with pancreatic cancer. When chemotherapy was added on tumor cell lines forcibly expressing the molecule, antitumor effect was compared with the control. Results: As a result of NGS analysis, we identified Olfactomedin-4 (OLFM4) molecule which was commonly shown high expression in chemotherapy administered PDXs. In IHC analysis, OLFM4 molecule expression was shown high expression with chemotherapy administered PDXs compared to untreated PDXs. For the analysis to use tumor cell lines forcedly expressing OLFM4 in vitro, the reduction rate of the tumor cell numbers was significantly lower than control vector, even if the concentration of the chemotherapy agent was increased. In a study using tissue specimens of 80 pancreatic cancer patients, Kaplan-Meier analysis showed that low expression of OLFM4 had a better survival rate than patients with high expression (p=0.0926, log-rank test). In multivariate analysis, it was shown that the high expression of OLFM4 was an independent poor prognostic factor with a statistically significant difference (p=0.044, Cox proportional hazards). Conclusions: It was demonstrated that high expression of OLFM4 was involved in chemoresistance and was an independent prognostic factor for pancreatic cancer. This molecule might be a candidate of therapeutic target in pancreatic cancer. Citation Format: Ryotaro Ohkuma, Erica Yada, Yutaro Kubota, Kazuyuki Hamada, Hiroo Ishida, Yuya Hirasawa, Hirotsugu Ariizumi, Etsuko Satoh, Junji Tsurutani, Kiyoshi Yoshimura, Tetsuro Sasada, Takeshi Aoki, Masahiko Murakami, Tomoko Norose, Nobuyuki Ohike, Masafumi Takimoto, Takuya Tsunoda, Satoshi Wada. High expression of Olfactomedin-4 correlates with chemoresistance and poor prognosis for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2146.