Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences/Peking Union Medical College, Beijing, China.
PLoS One. 2013 Dec 23;8(12):e82910. doi: 10.1371/journal.pone.0082910. eCollection 2013.
The extremely dismal prognosis of pancreatic cancer (PC) is attributed, at least in part, to lack of early diagnosis. Therefore, identifying differentially expressed genes in multiple steps of tumorigenesis of PC is of great interest. In the present study, a 7,12-dimethylbenzanthraene (DMBA)-induced PC model was established in male Sprague-Dawley rats. The gene expression profile was screened using an oligonucleotide microarray, followed by real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemical staining validation. A total of 661 differentially expressed genes were identified in stages of pancreatic carcinogenesis. According to GO classification, these genes were involved in multiple molecular pathways. Using two-way hierarchical clustering analysis, normal pancreas, acute and chronic pancreatitis, PanIN, early and advanced pancreatic cancer were completely discriminated. Furthermore, 11 upregulated and 142 downregulated genes (probes) were found by Mann-Kendall trend Monotone test, indicating homologous genes of rat and human. The qRT-PCR and immunohistochemistry analysis of CXCR7 and UBe2c, two of the identified genes, confirmed the microarray results. In human PC cell lines, knockdown of CXCR7 resulted in decreased migration and invasion. Collectively, our data identified several promising markers and therapeutic targets of PC based on a comprehensive screening and systemic validation.
胰腺癌（PC）预后极差，部分原因是缺乏早期诊断。因此，鉴定 PC 发生过程中多个步骤的差异表达基因具有重要意义。本研究采用 7,12-二甲基苯蒽（DMBA）建立雄性 Sprague-Dawley 大鼠 PC 模型。利用寡核苷酸微阵列筛选基因表达谱，然后通过实时定量聚合酶链反应（qRT-PCR）和免疫组织化学染色进行验证。在胰腺癌变过程的不同阶段共鉴定出 661 个差异表达基因。根据 GO 分类，这些基因参与了多个分子途径。采用双向层次聚类分析，可完全区分正常胰腺、急性和慢性胰腺炎、PanIN、早期和晚期胰腺癌。此外，通过 Mann-Kendall 趋势单调检验发现 11 个上调和 142 个下调基因（探针），表明这些基因与大鼠和人类的同源基因相似。对 CXCR7 和 UBe2c 这两个鉴定出的基因进行 qRT-PCR 和免疫组化分析，证实了微阵列结果。在人 PC 细胞系中，敲低 CXCR7 可导致迁移和侵袭减少。综上所述，我们的数据基于全面筛选和系统验证，鉴定了几个有希望的 PC 标志物和治疗靶点。
