Abstract
BACKGROUND:
Pancreatic adenocarcinoma is a malignancy with a dismal prognosis. Previous studies have suggested that in pancreatic cancer, human equilibrative nucleoside transporter 1 (hENT‐1) and ribonucleoside reductase subunit M1 (RRM1) expression may have prognostic value as well as predictive value with sensitivity to gemcitabine. This study investigated the prognostic value of hENT‐1 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‐1 and RRM1 expression levels in tumors were evaluated by quantitative reverse transcription‐polymerase chain reaction (QRT‐PCR), normalized to 2 reference genes, and expressed as ΔCt (low ΔCt 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‐1 (ΔCt > 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‐1 (ΔCt > 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. © 2011 American Cancer Society.