Sun Hongwei, Zhao Liang, Pan Kehua, Zhang Zhao, Zhou Mengtao, Cao Guoquan
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, P.R. China.
Oncol Rep. 2017 May;37(5):2779-2786. doi: 10.3892/or.2017.5526. Epub 2017 Mar 24.
In the present study, to investigate the potential molecular mechanism of pancreatic ductal adenocarcinoma (PDAC), mRNA and miRNA expression profiles were integrated for systematic analysis. Results showed that a total of 76 common differentially expressed genes (DEGs) were identified from 2 mRNA expression profiles that contained 39 tumor and 15 normal samples. Notably, the tumor and normal samples were able to be clearly classified into 4 groups based on the DEGs. mRNA‑miRNA regulation network analysis indicated that 22 out of the 76 DEGs including MUC4, RRM2 and CCL2 are regulated by 5 reported miRNAs. Survival analysis using SurvExpress database demonstrated that the common DEGs were able to significantly differentiate low- and high-risk PDAC groups in 4 datasets. In summary, various biological processes are probably involved in the development and progression of PDAC. Firstly, activation of MUC4 induces nuclear translocation of β-catenin and promotes the process of angiogenesis that provides necessary nutrition or oxygen for cancer cells. Then, RRM2 induces the invasiveness of PDAC via NF-κB. Finally, the formation of an immunosuppressive tumor microenvironment by recruiting regulatory T cells with high expression of CCL2 further promotes cancer cell proliferation and vascularization. Identification of valuable biological processes and genes can be helpful for the understanding of the molecular mechanism of PDAC.
在本研究中，为了探究胰腺导管腺癌（PDAC）潜在的分子机制，对mRNA和miRNA表达谱进行整合以进行系统分析。结果显示，从包含39个肿瘤样本和15个正常样本的2个mRNA表达谱中，共鉴定出76个常见的差异表达基因（DEG）。值得注意的是，基于这些DEG，肿瘤样本和正常样本能够被清晰地分为4组。mRNA-miRNA调控网络分析表明，76个DEG中的22个，包括MUC4、RRM2和CCL2，受5个已报道的miRNA调控。使用SurvExpress数据库进行的生存分析表明，这些常见的DEG能够在4个数据集中显著区分低风险和高风险的PDAC组。总之，多种生物学过程可能参与了PDAC的发生和发展。首先，MUC4的激活诱导β-连环蛋白的核转位，并促进为癌细胞提供必要营养或氧气的血管生成过程。然后，RRM2通过NF-κB诱导PDAC的侵袭性。最后，通过招募高表达CCL2的调节性T细胞形成免疫抑制性肿瘤微环境，进一步促进癌细胞增殖和血管生成。鉴定有价值的生物学过程和基因有助于理解PDAC的分子机制。
