Mao Yixiang, Shen Jianjun, Lu Yue, Lin Kevin, Wang Huamin, Li Yanan, Chang Ping, Walker Mary G, Li Donghui
Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou 215007, China.
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Oncotarget. 2017 Jun 27;8(26):42537-42547. doi: 10.18632/oncotarget.16451.
Gene expression microarrays have identified many tumor markers and therapeutic targets for pancreatic ductal adenocarcinoma (PDAC). However, microarray profilings have limited sensitivity and are prone to cross-hybridization between homologous DNA fragments. Here, we perform a transcriptome analysis of paired tumor and adjacent benign pancreatic tissues from 10 patients who underwent resection for PDAC. We identify a total of 2736 differentially expressed genes (DEGs) with false discovery rate less than 0.05, including 1554 upregulated, 1182 downregulated, and 6 microRNAs (miR-614, miR-217, miR-27b, miR-4451, miR-3609, and miR-612). Overexpression of five DEGs, i.e. KRT16, HOXA10, CDX1, SI, and SERPINB5 in tumors is confirmed by RT-PCR in 20 additional tissues. Overexpression of KRT16 in PDAC is also verified on protein level. In addition, top canonical pathways such as granulocyte adhesion and diapedesis pathway have been identified. Our study represents a comprehensive characterization of the PDAC transcriptome and provides insight to the mechanisms of pancreatic carcinogenesis and potential biomarkers and novel therapeutic targets for pancreatic cancer.
基因表达微阵列已鉴定出许多胰腺导管腺癌(PDAC)的肿瘤标志物和治疗靶点。然而,微阵列分析的灵敏度有限,且易于在同源DNA片段之间发生交叉杂交。在此,我们对10例接受PDAC切除术患者的配对肿瘤和相邻胰腺良性组织进行了转录组分析。我们共鉴定出2736个差异表达基因(DEG),其错误发现率小于0.05,其中包括1554个上调基因、1182个下调基因以及6个微小RNA(miR-614、miR-217、miR-27b、miR-4451、miR-3609和miR-612)。通过RT-PCR在另外20个组织中证实了肿瘤中5个DEG(即KRT16、HOXA10、CDX1、SI和SERPINB5)的过表达。KRT16在PDAC中的过表达在蛋白水平也得到了验证。此外,还鉴定出了诸如粒细胞黏附和渗出途径等顶级经典通路。我们的研究全面表征了PDAC转录组,并为胰腺癌的发生机制以及潜在生物标志物和新型治疗靶点提供了见解。