A molecular prognostic nomogram for resectable pancreatic cancer.

Abstract

154 Background: Defining clinically and biologically relevant phenotypes in other cancers has led to substantial improvements in the overall outcomes, but as yet none have been defined for pancreatic cancer (PC). About 80% of patients with pancreatic cancer succumb to the disease despite curative resection, many of whom within 6 months of surgery. There is a clear need to better define the biology and clinical behaviour of PC. This study aimed to evaluate the potential clinical utility of biologically relevant molecules as prognostic factors in resected PC. Methods: We assessed the relationship of aberrant S100A4 calcium-binding protein expression with survival in a cohort of 372 patients who underwent surgical resection for PC and derived a nomogram using clinicopathologic variables and aberrant expression of S100A4 and S100A2. Results: High S100A4 expression was an independent poor prognostic factor in both the training (n = 76; HR = 5.00, 95% CI = 2.29 – 10.9; p < 0.0001) and validation sets (n = 296; HR = 1.78, 95% CI = 1.29 – 2.46; p = 0.0004). Incorporating previously published data on S100A2, demonstrated that high expression of S100A4 was still an independent prognostic factor. Aberrant expression of these proteins stratified the cohort into three distinct prognostic groups. A preoperative nomogram using only variables that could be measured preoperatively (tumor size and molecular biomarkers), predicted survival better than nomograms derived from using clinicopathologic variables, which are only determined after examination of the resected specimen. Conclusions: Aberrant expression of S100A4 and S100A2 stratifies PC into distinct prognostic groups and improves the accuracy of prognostic nomograms using variables that can be determined preoperatively. The development and application of such nomograms in routine clinical practice has the potential to improve patient selection and as a consequence overall outcomes for PC. No significant financial relationships to disclose.