MicroRNA profiling of diagnostic needle aspirates from patients with pancreatic cancer.
MicroRNA profiling of diagnostic needle aspirates from patients with pancreatic cancer.
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DOI：
10.1038/bjc.2012.383
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发表时间：
2012-10-09
影响因子：
8.8
通讯作者：
Philip, P. A.
中科院分区：
文献类型：
--
作者：
Ali, S.;Saleh, H.;Sethi, S.;Sarkar, F. H.;Philip, P. A.
开发胰腺癌（PC）生物标志物的一个主要挑战是在诊断时获得的少量组织。单基因分析可能无法可靠地预测PC的生物学，因为其复杂的分子组成。microRNA（miRNA）分析可以提供更多信息的肿瘤分子询问。本研究的主要目的是确定从细针抽吸物（FNA）获得的存档福尔马林固定石蜡包埋（FFPE）细胞块进行miRNA阵列和定量实时PCR（qRT-PCR）的可行性，FNA是疑似PC的最常见诊断程序。对来自可疑胰腺肿块的FNA的FFPE进行MicroRNA表达谱分析。受试者包括病理诊断为胰腺癌的受试者和其他非恶性胰腺组织学受试者。采用qRT-PCR检测miRNA的表达水平，并对miRNA的异常表达进行验证。分别共有29例和15例受试者患有胰腺癌，无癌症证据。每位患者的RNA产量从25 ng到100 ng不等。分析表明胰腺癌中超过228种miRNA的失调，其中前7种通过qRT-PCR进一步验证。let-7 c、let-7 f和miR-200 c的表达在大多数患者中显著降低，而miR-486- 5 p和miR-451的表达在所有胰腺癌患者中显著升高。microRNAs let-7 d和miR-423- 5 p下调或上调，其表达存在显著的个体间差异。这项研究证明了使用来自FNA的存档FFPE细胞块建立胰腺癌特有的基于RNA的分子特征的可行性，其在临床试验中具有潜在的应用，用于风险分层，患者选择和靶点验证。
A major challenge to the development of biomarkers for pancreatic cancer (PC) is the small amount of tissue obtained at the time of diagnosis. Single-gene analyses may not reliably predict biology of PC because of its complex molecular makeup. MicroRNA (miRNA) profiling may provide a more informative molecular interrogation of tumours. The primary objective of this study was to determine the feasibility of performing miRNA arrays and quantitative real-time PCR (qRT–PCR) from archival formalin-fixed paraffin-embedded (FFPE) cell blocks obtained from fine-needle aspirates (FNAs) that is the commonest diagnostic procedure for suspected PC. MicroRNA expression profiling was performed on FFPE from FNA of suspicious pancreatic masses. Subjects included those who had a pathological diagnosis of pancreatic adenocarcinoma and others with a non-malignant pancreatic histology. Exiqon assay was used to quantify miRNA levels and qRT–PCR was used to validate abnormal expression of selected miRNAs. A total of 29 and 15 subjects had pancreatic adenocarcinoma and no evidence of cancer, respectively. The RNA yields per patient varied from 25 to 100 ng. Profiling demonstrated deregulation of over 228 miRNAs in pancreatic adenocarcinoma of which the top 7 were further validated by qRT–PCR. The expression of let-7c, let-7 f, and miR-200c were significantly reduced in most patients whereas the expression of miR-486-5p and miR-451 were significantly elevated in all pancreas cancer patients. MicroRNAs let-7d and miR-423-5p was either downregulated or upregulated with a significant inter-individual variation in their expression. This study demonstrated the feasibility of using archival FFPE cell blocks from FNAs to establish RNA-based molecular signatures unique to pancreatic adenocarcinoma with potential applications in clinical trials for risk stratification, patient selection, and target validation.
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影响因子：
3.5
作者：
Goswami RS;Waldron L;Machado J;Cervigne NK;Xu W;Reis PP;Bailey DJ;Jurisica I;Crump MR;Kamel-Reid S
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作者：
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影响因子：
21.3
作者：
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