Pancreatic ductal adenocarcinoma (PDAC) is largely heterogeneous. We sought to develop and validate a signature to precisely predict chemotherapy sensitivity in PDAC. Genetic events of the four most commonly mutated genes in PDAC and expressions of 12 PI3K/AKT/mTOR pathway markers were examined in consecutive patients with PDAC. A 9-feature signature for prediction of chemotherapy benefits was constructed using the LASSO Cox regression model, and validated in two independent cohorts.

Inclusion Criteria:

• ECOG performance status score of 0-1 before resection
• complete clinicopathologic and follow-up data
• availability of formalin-fixed paraffin-embedded (FFPE) specimens of resected primary tumor and hematoxylin and eosin slides with invasive tumor components

Exclusion Criteria:

• any previous history of cancer
• any anticancer therapy prior to resection or adjuvant radiotherapy
• metastatic cases
• major postsurgical complications with Clavien-Dindo Grade ≥2

Consecutive patients with incident, primary, microscopically-confirmed nonmetastatic PDAC who underwent resection were initially enrolled.