High E2F7 Expression Indicates Pancreatic Cancer Aggressiveness and Downregulation of E2F7 Enhances Sensitivity to S-1.

[BACKGROUND] Pancreatic cancer (PC) remains a highly lethal disease with few reliable biomarkers to guide chemotherapy choices. New biomarkers for selecting anticancer drugs are needed to enhance the effectiveness of current multimodal treatment approaches. This study aimed to find a new biomarker by using clinical data and specimens collected for a Japanese randomized controlled trial (RCT).

[METHODS] Gene expression array analysis was performed using PC tissues collected for the ancillary research of JASPAC01, a nationwide phase 3 RCT of adjuvant chemotherapy for patients with PC in Japan. A candidate gene was validated using tissue and blood samples from a second PC patient cohort undergoing radical surgery at the authors' institution. Additionally, experiments were performed with cancer cell lines to investigate the functions of the candidate gene.

[RESULTS] Expression of E2F7 mRNA was the most influential prognostic factor of postoperative overall survival outcomes in the primary tissue-available cases in the JASPAC01 cohort (hazard ratio [HR], 1.386; 95% confidence interval [CI], 1.005-1.912; p = 0.045). High E2F7 expression itself correlates with poor survival outcomes (p = 0.045 for OS). Moreover, the benefits of adjuvant S-1 treatment were reduced in high E2F7 cases (p = 0.042 for OS; p = 0.007 for RFS). In vitro experiments demonstrated that E2F7 inhibition suppressed cancer cell proliferation and minimized the 50% inhibitory concentration of S-1.

[CONCLUSIONS] Tissue mRNA expression levels of E2F7 correlated with patient prognosis in PC. In the low E2F7 mRNA expression group, patients who received S-1 as adjuvant chemotherapy had a better prognosis than those who received gemcitabine (GEM).