Predictive and prognostic roles of ribonucleotide reductase M1 in resectable pancreatic adenocarcinoma.
BACKGROUND
Ribonucleotide reductase M1 (RRM1) is an important molecule in different types of cancer. The objective of this study was to evaluate the predictive roles of RRM1 in the survival of patients with resectable pancreatic adenocarcinoma who received treatment with gemcitabine or nongemcitabine adjuvant therapy.


METHODS
In total, 122 patients underwent tumor resection for pancreatic adenocarcinoma at the authors' institution from October 1999 to December 2007. Total RNA was isolated from microdissected, paraffin-embedded tumors. RRM1 expression levels were measured using quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) and were dichotomized using recursive partitioning analysis. The Kaplan-Meier method was used to estimate overall survival and progression-free survival, and the predictive value of RRM1 expression on survival was examined using Cox proportional hazards regression.


RESULTS
RRM1 expression did not have significant prognostic value in the entire cohort regarding overall survival (P = .2) or progression-free survival (P = .7). In the subgroup of 44 patients who received adjuvant gemcitabine, patients who had low RRM1 expression had longer overall survival (median, 47.8 months vs 14.1 months; P = .005) and a trend toward longer progression-free survival (median not reached vs 12.9 months; P = .06). In contrast, in the subgroup of 35 patients who received nongemcitabine adjuvant therapy, patients who had high RRM1 expression had significantly longer overall survival (median, 41.9 months vs 19.8 months; P = .01) and progression-free survival (median, 70.0 months vs 11.8 months; P = .04). These results were confirmed in Cox proportional hazards multivariable analysis.


CONCLUSIONS
In patients with resectable pancreatic adenocarcinoma, low RRM1 expression in the tumor predicted an overall survival benefit of adjuvant gemcitabine; and high RRM1 expression predicted the survival benefit of nongemcitabine adjuvant therapy.
Department of Anatomic Pathology, The Cleveland Clinic, Ohio, USA.
Hao
H
Xie
Wei
W
Jiang
John
J
Jiang
Yixin
Y
Wang
Richard
R
Kim
Xiaobo
X
Liu
Xiuli
X
Liu
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D012262:Ribonucleoside Diphosphate Reductase; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D000093542:Gemcitabine