Identification of laminin γ2 as a prognostic and predictive biomarker for determining response to gemcitabine-based therapy in pancreatic ductal adenocarcinoma.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. While the extracellular matrix component plays an integral role in PDAC pathogenesis and mediating chemoresistance, its role in predicting response to chemotherapy in patients with PDAC remains unclear. Methods We performed a systematic biomarker discovery by analysing genome-wide transcriptomic profiling data from 423 patients (GSE71729, GSE21501 and The Cancer Genome Atlas [TCGA]) for predicting overall survival (OS). This was subsequently validated in two independent clinical cohorts of 270 patients with PDAC (training cohort, n = 121, and validation cohort, n = 149). In addition, we investigated endoscopic ultrasound-fine needle aspiration biopsy specimens from 51 patients with PDAC with an unresectable cancer for predicting therapeutic response to gemcitabine-based therapy. Results After rigorous bioinformatic analysis, we identified laminin γ2 (LAMC2) to be a significant prognostic factor in all three PDAC data sets (GSE71729: hazard ratio [HR] = 2.04, P = 0.002; GSE21501: HR = 2.17, P = 0.031; TCGA: HR = 2.57, P  Conclusion We conclude that LAMC2 is a novel prognostic and predictive biomarker for gemcitabine-based therapy in both the adjuvant and palliative setting; which could have significant impact on precision and individualised treatment of patients with PDAC.