Gene Expression Levels as Predictive Markers of Outcome in Pancreatic Cancer after Gemcitabine-Based Adjuvant Chemotherapy
Gene Expression Levels as Predictive Markers of Outcome in Pancreatic Cancer after Gemcitabine-Based Adjuvant Chemotherapy
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DOI：
10.1593/neo.10458
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发表时间：
2010-10-01
期刊：
影响因子：
4.8
通讯作者：
Tanaka, Masao
中科院分区：
文献类型：
--
作者：
Fujita, Hayato;Ohuchida, Kenoki;Tanaka, Masao
背景和目的：胰腺导管腺癌（PDAC）的标准姑息化疗是基于吉西他滨的化疗;然而，PDAC仍然是一个重大的治疗挑战。本研究的目的是研究切除的PDAC组织中涉及吉西他滨敏感性的基因的表达模式，并确定基因表达与治疗结果的相关性。材料和方法：我们从70例PDAC患者中获得福尔马林固定石蜡包埋（FFPE）组织样本。在70例患者中，40例接受了基于吉西他滨的辅助化疗（AC）。我们通过定量实时逆转录聚合酶链反应测定hENT 1、dCK、CDA、RRM 1和RRM 2信使RNA（mRNA）水平，并根据hENT 1、dCK、RRM 1和RRM 2的表达水平确定综合评分（GEM评分），以研究与生存时间的相关性。通过确定这些基因在内镜超声引导下细针穿刺（EUS-FNA）细胞学标本中的表达水平，我们研究了个体化化疗的可行性。研究结果：在吉西他滨治疗组中，高dCK（P = 0.0067）、低RRM 2（P = 0.003）和高GEM评分（P = 0.0003）组的无病生存期显著延长。一个低的GEM分数（
BACKGROUND AND AIMS: The standard palliative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) is gemcitabine-based chemotherapy; however, PDAC still presents a major therapeutic challenge. The aims of this study were to investigate the expression pattern of genes involved in gemcitabine sensitivity in resected PDAC tissues and to determine correlations of gene expression with treatment outcome. MATERIALS AND METHODS: We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 70 patients with PDAC. Of the 70 patients, 40 received gemcitabine-based adjuvant chemotherapy (AC). We measured hENT1, dCK, CDA, RRM1, and RRM2 messenger RNA (mRNA) levels by quantitative real-time reverse transcription-polymerase chain reaction and determined the combined score (GEM score), based on the expression levels of hENT1, dCK, RRM1, and RRM2, to investigate the association with survival time. By determining the expression levels of these genes in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytologic specimens, we investigated the feasibility of individualized chemotherapy. RESULTS: High dCK (P = .0067), low RRM2 (P = .003), and high GEM score (P = .0003) groups had a significantly longer disease-free survival in the gemcitabine-treated group. A low GEM score (