核苷酸还原酶 M1 在可切除胰腺腺癌中的预测和预后作用。

Predictive and prognostic roles of ribonucleotide reductase M1 in resectable pancreatic adenocarcinoma.

机构信息

Department of Anatomic Pathology, The Cleveland Clinic, Ohio, USA.

出版信息

Cancer. 2013 Jan 1;119(1):173-81. doi: 10.1002/cncr.27715. Epub 2012 Jun 26.

DOI:10.1002/cncr.27715

PMID:22736490

Abstract

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.

摘要

背景

核糖核苷酸还原酶 M1（RRM1）是不同类型癌症中的一种重要分子。本研究旨在评估 RRM1 在接受吉西他滨或非吉西他滨辅助治疗的可切除胰腺腺癌患者生存中的预测作用。

方法

作者所在机构于 1999 年 10 月至 2007 年 12 月对 122 例胰腺腺癌患者进行了肿瘤切除术。从微切割、石蜡包埋的肿瘤中分离总 RNA。使用定量逆转录-聚合酶链反应（QRT-PCR）测量 RRM1 表达水平，并使用递归分区分析将其分为二项式。使用 Kaplan-Meier 方法估计总生存率和无进展生存率，并使用 Cox 比例风险回归检查 RRM1 表达对生存率的预测价值。

结果

在整个队列中，RRM1 表达在总生存率（P =.2）或无进展生存率（P =.7）方面均无显著预后价值。在接受辅助吉西他滨治疗的 44 例患者亚组中，RRM1 低表达患者的总生存率更长（中位数，47.8 个月 vs 14.1 个月；P =.005），无进展生存率呈延长趋势（中位数未达到 vs 12.9 个月；P =.06）。相比之下，在接受非吉西他滨辅助治疗的 35 例患者亚组中，RRM1 高表达患者的总生存率（中位数，41.9 个月 vs 19.8 个月；P =.01）和无进展生存率（中位数，70.0 个月 vs 11.8 个月；P =.04）均显著延长。这些结果在 Cox 比例风险多变量分析中得到证实。