Low Expression of Ribonucleotide Reductase M1 Predicts Adjuvant Gemcitabine Treatment Benefit in Patients with Resectable Pancreatic Adenocarcinoma
Hao Xie, Wei Jiang, John Jiang, Yixin Wang, Richard Kim, Xiuli Liu. Cleveland Clinic, Cleveland; Veridex LLC, Johnson & Johnson Company, San Diego; Moffitt Cancer Center, Tampa
Background: Gemcitabine has been a cornerstone of current chemotherapy for pancreatic cancer. Our previous pilot study in 18 patients suggested low expression of RRM1 was predictive of adjuvant gemcitabine treatment benefit in patients with resectable pancreatic adenocarcinoma (W Jiang et al., Mod Path 23:357A, 2010). This study aims to confirm our previous finding in a larger cohort of patients.
Design: 122 patients underwent pancreatic resection at our institution for resectable pancreatic adenocarcinoma from 10/1999 to 12/2007; 44 of them received adjuvant gemcitabine treatment prior to disease recurrence/metastases. Total RNA was isolated from micro-dissected paraffin-embedded tumors. The expression of RRM1 in tumors was determined by QRT-PCR and the expression levels were normalized to two endogenous reference genes and stratified into high expression group and low expression group using recursive partitioning analysis. Overall survival (OS) and progression-free survival (PFS) of these two groups were estimated with the Kaplan-Meier method. The prognostic value of RRM1 expression on OS and PFS was examined with Cox proportion hazards analysis.
Results: RRM1 expression did not have prognostic value in the entire cohort of patients regarding OS (p=0.14) and PFS (p=0.68). However, in the subgroup of 44 patients who received gemcitabine treatment as an adjuvant therapy, patients with low RRM1 expression had significantly longer OS (median OS 44.4 vs. 14.5 months; p=0.01, figure A). While Cox proportion hazards multivariate analysis identified number of positive lymph nodes and perineural invasion as predictors of shorter OS (HR 1.18, p=0.02) and shorter PFS (HR 3.5, p=0.004), respectively, it confirmed that low expression of RRM1 was associated with longer OS (HR 0.35, p=0.009) and PFS (HR 0.37, p=0.004).
Conclusions: Low RRM1 expression determined by QRT-PCR on paraffin-embedded pancreatic carcinoma tissue in patients who received gemcitabine as an adjuvant treatment predicts a progression-free and overall survival benefit.
Monday, March 19, 2012 8:15 AM
Platform Session: Section G1, Monday Morning