Stromal MicroRNA-21 Levels Predict Response to 5-Fluorouracil in Patients With Pancreatic Cancer

被引:40
|
作者
Donahue, Timothy R. [1 ,2 ]
Nguyen, Andrew H. [1 ]
Moughan, Jennifer [3 ]
Li, Luyi [1 ]
Tatishchev, Sergei [4 ]
Toste, Paul [1 ]
Farrell, James J. [5 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[3] RTOG Stat Dept, Philadelphia, PA USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA
[5] Yale Univ, Sch Med, Yale Ctr Pancreat Dis, New Haven, CT USA
关键词
biomarkers; pancreatic cancer; microRNA-21; 5-fluorouracil; II COLON-CANCER; BREAST-CANCER; CHEMORESISTANCE; RESISTANCE; INVASION; ADENOCARCINOMA; GEMCITABINE; METASTASIS; MIR-21; STAGE;
D O I
10.1002/jso.23750
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background and ObjectivesMicroRNA-21 (miR-21) is upregulated and inversely associated with survival in many cancer types, including pancreatic ductal adenocarcinoma (PDAC). We studied the predictive value of miR-21 levels for gemcitabine or 5-fluorouracil (5-FU) response in tumor cells (TCs) or cancer associated fibroblasts (CAFs) in a cohort of PDAC patients from the RTOG 9704 trial. MethodsMiR-21 expression in CAFs and TCs, determined by in situ hybridization, of the 229 PDAC subset from RTOG 9704 was correlated with (i) histopathology characteristics using a chi-square test; and (ii) patient overall survival (OS) using the Cox proportional hazards model. ResultsMiR-21 was strongly expressed in TCs and CAFs in 137/182 (75%) and 152/181 (84%) PDACs, respectively. MiR-21 expression in CAFs for the group given 5-FU for OS: (i) approached significance in a univariate analysis (hazard ratio [HR], 1.57; 95% confidence interval [CI], 0.95-2.57; P=0.07); and (ii) was significant in the multivariate model (HR, 1.70; 95% CI, 1.03-2.82; P=0.038). ConclusionsMiR-21 expression in CAFs was associated with decreased OS in PDAC patients who received 5-FU, but not gemcitabine. These findings begin to identify stromal miR-21 as a marker to guide chemotherapy choice in PDAC patients. J. Surg. Oncol. 2014; 110:952-959. (c) 2014 Wiley Periodicals, Inc.
引用
收藏
页码:952 / 959
页数:8
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