Prognostic Roles of Human Equilibrative Transporter 1 (hENT-1) and Ribonucleoside Reductase Subunit M1 (RRM1) in Resected Pancreatic Cancer

BACKGROUND: Pancreatic adenocarcinoma is a malignancy with a dismal prognosis. Previous studies have suggested that in pancreatic cancer, human equilibrative nucleoside transporter 1 (hENT-7) and ribonucleoside reductase subunit M1 (RPM) expression may have prognostic value as well as predictive value with sensitivity to gemcitabine. This study investigated the prognostic value of hENT-7 and RRM1 expression in resected pancreatic cancer. METHODS: Eighty-four patients who underwent pancreaticoduodenectomy from 2000 to 2005 were included in this study. Patients were followed for a median of 60 months (range, 44-110). Total RNA was isolated from macrodissected paraffin-embedded tumors. hENT-7 and RPM1 expression levels in tumors were evaluated by quantitative reverse transcription-polymerase chain reaction (QRT-PCR), normalized to 2 reference genes, and expressed as Delta Ct (low Delta Ct means high expression). Univariate and multivariable prognostic factors for overall survival (OS) and progression-free survival (PFS) were identified via Cox proportional hazards analysis. RESULTS: Univariate analysis identified hENT-1, overall stage, lymphovascular invasion, perineural invasion, and adjuvant therapy as prognostic factors for both PFS and OS. Multivariate analysis confirmed the association of low expression of hENT-7 (Delta Ct > 0.2027) (P = .007), perineural invasion (P = .021), and lack of adjuvant treatment (P < 0.001) with worse OS. Multivariate analysis also confirmed the association of low expression of hENT-7 (Delta Ct > 0.5391) with worse PFS (P = .016) in addition to overall stage (P = .013), perineural invasion (P = .042), and lack of adjuvant treatment (hazard ratio 2.31, P = .029). RRM1 expression was not associated with OS or PFS in the current cohort. CONCLUSIONS: Low expression of hENT-1 was associated with worse OS and PFS in patients with resected pancreatic adenocarcinoma independent of gemcitabine therapy. Cancer 2011;117:3126-34. (C) 2077 American Cancer Society.