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高 EGFR mRNA 表达是吉西他滨为基础的辅助化疗后胰腺癌生存时间降低的预后因素。

High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy.

机构信息

Department of Surgery and Oncology, Kyushu University, Fukuoka, Japan.

出版信息

Int J Oncol. 2011 Mar;38(3):629-41. doi: 10.3892/ijo.2011.908. Epub 2011 Jan 17.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) still presents a major therapeutic challenge and a phase III clinical trial has revealed that the combination of gemcitabine and a human epidermal growth factor receptor type I (HER1/EGFR) targeting agent presented a significant benefit compared to treatment with gemcitabine alone. The aim of this study was to investigate EGFR mRNA expression in resected PDAC tissues and its correlation with patient prognosis. We obtained formalin-fixed paraffin-embedded (FFPE) tissue samples from 88 patients with PDAC who underwent pancreatectomy, and measured EGFR mRNA levels by quantitative real-time reverse transcription-polymerase chain reaction. The high-level EGFR group had significantly shorter disease-free-survival (p=0.029) and overall-survival (p=0.014) as shown by univariate analyses, although these did not reach statistical significance, as shown by multivariate analyses. However, we found that high EGFR expression was an independent prognostic factor in patients receiving gemcitabine-based adjuvant chemotherapy (p=0.023). Furthermore, we measured EGFR mRNA levels in 20 endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) cytological specimens. Altered EGFR levels were distinguishable in microdissected neoplastic cells from EUS-FNA cytological specimens compared to those in whole cell pellets. In conclusion, quantitative analysis of EGFR mRNA expression using FFPE tissue samples and microdissected neoplastic cells from EUS-FNA cytological specimens could be useful in predicting prognosis and sensitivity to gemcitabine in PDAC patients.

摘要

胰腺导管腺癌(PDAC)仍然是一个主要的治疗挑战,一项 III 期临床试验表明,与单独使用吉西他滨相比,吉西他滨联合表皮生长因子受体 I 型(HER1/EGFR)靶向药物治疗具有显著益处。本研究旨在研究切除的 PDAC 组织中的 EGFR mRNA 表达及其与患者预后的关系。我们从 88 例接受胰腺切除术的 PDAC 患者中获得了福尔马林固定石蜡包埋(FFPE)组织样本,并通过定量实时逆转录-聚合酶链反应测量了 EGFR mRNA 水平。单因素分析显示,高水平 EGFR 组的无病生存期(p=0.029)和总生存期(p=0.014)明显缩短,尽管多因素分析显示这些结果没有达到统计学意义。然而,我们发现高 EGFR 表达是接受基于吉西他滨的辅助化疗的患者的独立预后因素(p=0.023)。此外,我们测量了 20 例内镜超声引导下细针抽吸(EUS-FNA)细胞学标本中的 EGFR mRNA 水平。与全细胞沉淀相比,从 EUS-FNA 细胞学标本中微分离的肿瘤细胞中可以区分 EGFR 水平的改变。总之,使用 FFPE 组织样本和从 EUS-FNA 细胞学标本中微分离的肿瘤细胞对 EGFR mRNA 表达进行定量分析可能有助于预测 PDAC 患者的预后和对吉西他滨的敏感性。

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