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-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.
Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio, USA. Richard.kim@moffitt.org
Richard
R
Kim
Ann
A
Tan
Kevin K
KK
Lai
John
J
Jiang
Yixen
Y
Wang
Lisa A
LA
Rybicki
Xiulu
X
Liu
D000230:Adenocarcinoma / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D033721:Equilibrative Nucleoside Transporter 1 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D033721:Equilibrative Nucleoside Transporter 1; C438649:SLC29A1 protein, human; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine