Abstract 2514: Adjuvant chemotherapy drug response-related gene detection using JASPAC01 pancreatic cancer resection cohort

Abstract Background of Purpose: Although various multidisciplinary treatments have been attempted for pancreatic cancer, sufficient improvement in prognosis has not been achieved. It is necessary to establish biomarkers that can predict the malignant potential for each patient and the therapeutic effect of chemotherapy in order to select the optimal treatment for each individual case.This study was designed as a companion study to the phase III comparative study (JASPAC 01 of gemcitabine (GEM) and S-1 therapy as adjuvant chemotherapy after pancreatectomy. Among the 22 candidate biomarker genes that have been reported to be involved in pancreatic cancer treatment prognosis, we focused on E2F transcription factor 7 (E2F7), which is associated with a significantly poor overall survival rate when highly expressed. E2F7 is one of the target proteins of p53 and has been reported to be involved in cell cycle regulation. We examined the possibility of E2F7 expression in pancreatic cancer surgery and the effect of adjuvant chemotherapy. Patients and Methods: After optimizing the E2F7 imunostaining protocol, we scored E2F7 protein expression using the slides from excised tissues from JASPAC 01 registered cases. We investigated the relationship between malignancy and treatment efficacy using the case cohort treatment allocation information, clinicopathological information, and prognosis data. Results: Immunostaining was performed on approximately 330 resected pancreatic cancer specimens from 24 facilities nationwide. Of the 311 patients for whom E2F7 protein expression could be scored, 202 patients who completed the assigned treatment were included in the analysis. In 88 cases with high E2F7 expression, no significant difference in clinicopathological factors was observed between the S-1 treatment group and the GEM treatment group, but the S-1 treatment group showed better recurrence-free survival (RFS, P=0.066) and overall survival (OS, P=0.015) were observed. On the other hand, in the 114 patients with low E2F7 expression, there was no significant difference in clinicopathological factors between the two groups (RFS, P=0.168, OS: P=0.276). High E2F7 expression in pancreatic cancer tissues may affect S-1 sensitivity, GEM resistance, or both. Conclusions: It is considered that high expression E2F7 in pancreatic cancer may affect the therapeutic efficacy of GEM and S-1, which are frequently used in adjuvant chemotherapy for pancreatic cancer. Citation Format: Yukiyasu Okamura, Tomohisa Otsu, Masamichi Hayashi, Ryo Ashida, Katsuhiko Uesaka. Adjuvant chemotherapy drug response-related gene detection using JASPAC01 pancreatic cancer resection cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2514.