Abstract
Objective:We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection.Background:Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease.Method:In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram.Results:High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables.Conclusions:Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.
Highlights
Using RNA sequencing and methylation arrays, we recently reported hypomethylation of S100A2 is associated with the prognostic ‘‘Squamous’’ subtype of pancreatic ductal adenocarcinoma (PDAC).[20]
We assess and validate the prognostic value of these 2 molecules in 1184 patients. Aberrant expression of these biomarkers stratify patients with resectable pancreatic cancer into 3 distinct prognostic groups in a training set (n 1⁄4 518) and form the basis of a biomarker-based preoperative nomogram aimed at identifying those at high risk of early recurrence
In all 3 cohorts, high expression of S100A2 calcium-binding protein was associated with poor survival after pancreatectomy
Summary
We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. Background: we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease. Method: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants 1⁄4 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram
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