Role of Inflammation in the Development and Progression of Pancreatic Cancer

在我们最初的方法中，我们通过定量RT/PCR分析了27例快速冷冻胰腺导管腺癌（PDAC）样本中25个炎症基因和9个mirna的表达。其中18例患者的非肿瘤胰腺周围也进行了检查。我们的实验室早期研究了所选的25种炎症基因表达，以确定它们在结肠癌中的预后意义。9个miRNA的选择是基于之前报道的它们在胰腺癌中的差异表达。我们的初步数据显示，巨噬细胞迁移抑制因子（MIF）、IL-23、Annexin A1和miR-210的表达增加与预后不良相关。我们目前正在一个独立的PDAC队列中验证这些结果。在我们对FOX转录因子在胰腺癌中的作用的研究中，我们有初步的数据显示，与PDAC患者的非肿瘤组织相比，肿瘤组织中FOXA3的表达较低。这一观察结果在PDAC病例的独立队列中得到进一步验证。目前，我们正在研究FOXA3在胰腺癌细胞系中过表达和敲除策略在胰腺癌发生发展中的潜在作用。我们的研究还发现，在PDAC病例中，FOXL1的低表达与较差的生存率相关。我们目前正在一个独立的PDAC病例队列中验证这一发现。最后，通过免疫组织化学染色，我们发现在PDAC病例中，与周围非肿瘤组织相比，肿瘤中表达细胞质磷酸化foxo3的细胞数量显著增加。这一观察结果正在PDAC病例的独立队列中得到验证。

In our initial approach, the expression of 25 inflammatory genes and 9 miRNAs were analyzed by quantitative RT/PCR in snap-frozen pancreatic ductal adenocarcinoma (PDAC) samples from 27 cases. In 18 of these cases surrounding non-tumorous pancreas from the same patients were also examined. The selected 25 inflammatory gene expression were earlier investigated in our laboratory to determine their prognostic significance in colon cancer. The selection of 9 miRNA was based on their differential expression in pancreatic cancer as reported earlier. Our preliminary data shows that an increased expression of macrophage migration inhibitory factor (MIF), IL-23, Annexin A1 and miR-210 is associated with poorer prognosis. We are currently validating these results in an independent cohort of PDAC. In our investigation of the role of FOX transcription factors in pancreatic cancer, we have preliminary data showing a lower expression of FOXA3 in tumors as compared to non-tumor tissue in the patients with PDAC. This observation was further validated in an independent cohort of PDAC cases. Currently, we are investigating the potential role of FOXA3 in the development and progression of pancreatic cancer by applying over- expression and knock-down strategy in pancreatic cancer cell lines. Our investigations also found that a lower expression of FOXL1 is associated with poorer survival in PDAC cases. We are currently validating this finding in an independent cohort of PDAC cases. Lastly, we found that a significantly higher number of cells expressed cytoplasmic phosphorylated-FOXO3 in tumors as compared to the surrounding nontumor tissue in PDAC cases as determined by immunohistochemical staining. This observation is being validated in an independent cohort of PDAC cases.