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肿瘤内人嘧啶核苷转运蛋白 1(hENT1)和核糖核苷酸还原酶调节亚基 M1(RRM1)表达的联合分析是手术切除后接受辅助吉西他滨为基础化疗的胰腺癌患者生存的有力预测指标。

Combined analysis of intratumoral human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) expression is a powerful predictor of survival in patients with pancreatic carcinoma treated with adjuvant gemcitabine-based chemotherapy after operative resection.

机构信息

Department of Surgery, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.

出版信息

Surgery. 2013 Apr;153(4):565-75. doi: 10.1016/j.surg.2012.10.010. Epub 2012 Dec 17.

DOI:10.1016/j.surg.2012.10.010
PMID:23253379
Abstract

BACKGROUND

Although postoperative adjuvant chemotherapy for pancreatic carcinoma improves survival in some patients, its efficacy varies among individuals. The aim of this study was to determine the usefulness of intratumoral expression of human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase regulatory subunit M1 (RRM1) as predictive markers of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection.

METHODS

The expression of intratumoral hENT1 and RRM1 was examined immunohistochemically in 109 patients with pancreatic carcinoma who received adjuvant gemcitabine-based chemotherapy after operative resection. Relationships between clinicopathologic factors, including hENT1 and RRM1 expression, and disease-free and overall survival (DFS and OS) were evaluated by univariate and multivariate analyses.

RESULTS

The 5-year DFS and OS rates for the 109 patients were 26% and 31%, respectively. In univariate analysis, both hENT1 and RRM1 expression were significantly associated with DFS (hENT1, P = .004; RRM1, P = .011) and OS (hENT1, P = .001; RRM1, P = .040). In multivariate analysis, both were independent factors for DFS (hENT1, P = .001; RRM1, P = .009) and OS (hENT1, P = .001, RRM1, P = .019). Evaluation of the combination analysis of both was also identified as a powerful independent predictor of DFS (P < .001) and OS (P < .001).

CONCLUSION

Expression of hENT1 and RRM1 is predictive of the efficacy of adjuvant gemcitabine-based chemotherapy for pancreatic carcinoma after operative resection. In addition, their combined analysis has greater predictive value than either factor alone.

摘要

背景

尽管胰腺癌术后辅助化疗可改善部分患者的生存情况,但疗效存在个体差异。本研究旨在确定肿瘤内人嘧啶核苷转运蛋白 1(hENT1)和核糖核苷酸还原酶调节亚基 M1(RRM1)的表达作为接受手术切除后接受吉西他滨为基础的辅助化疗的胰腺癌患者疗效的预测标志物的有用性。

方法

对 109 例接受手术切除后接受吉西他滨为基础的辅助化疗的胰腺癌患者的肿瘤内 hENT1 和 RRM1 表达进行免疫组化检测。通过单因素和多因素分析评估包括 hENT1 和 RRM1 表达在内的临床病理因素与无病生存(DFS)和总生存(OS)之间的关系。

结果

109 例患者的 5 年 DFS 和 OS 率分别为 26%和 31%。单因素分析显示,hENT1 和 RRM1 表达均与 DFS(hENT1,P =.004;RRM1,P =.011)和 OS(hENT1,P =.001;RRM1,P =.040)显著相关。多因素分析显示,hENT1 和 RRM1 均为 DFS(hENT1,P =.001;RRM1,P =.009)和 OS(hENT1,P =.001,RRM1,P =.019)的独立因素。对两者联合分析也被确定为 DFS(P <.001)和 OS(P <.001)的强有力的独立预测因子。

结论

hENT1 和 RRM1 的表达可预测接受手术切除后接受吉西他滨为基础的辅助化疗的胰腺癌患者的疗效。此外,两者联合分析的预测价值大于任一因素单独分析。

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