The integrated pathway of TGFβ/Snail with TNFα/NFκB may facilitate the tumor-stroma interaction in the EMT process and colorectal cancer prognosis.
The integrated pathway of TGFβ/Snail with TNFα/NFκB may facilitate the tumor-stroma interaction in the EMT process and colorectal cancer prognosis.
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TGF beta/Snail 与 TNF α/NF kappa B 的整合途径可能促进 EMT 过程和结直肠癌预后中的肿瘤-基质相互作用
DOI：
10.1038/s41598-017-05280-6
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发表时间：
2017-07-07
影响因子：
4.6
通讯作者：
Lai M
中科院分区：
文献类型：
--
作者：
Li H;Zhong A;Li S;Meng X;Wang X;Xu F;Lai M
大量证据表明，上皮-间充质转化(EMT)在结直肠癌(CRC)的发生发展和预后中起着重要作用。为了揭示在癌细胞与其微环境的协同作用中发挥作用的关键调控因子，从而影响EMT过程，我们对结直肠癌标本进行了系统的分析和预后评估。用激光显微切割术捕捉肿瘤芽及其周围间质。我们利用基因表达谱、生物信息学分析和调控网络构建进行分子选择。探讨潜在生物标志物的临床意义。BGN、MMP1、LGALS1、SERPINB5和TM4SF4参与了转化生长因子β/Snail与肿瘤坏死因子α/核因子κB的整合通路，并与结直肠癌患者的预后有关。这些个体潜在生物标记物的高表达患者预后较差。在已鉴定的生物标志物中，BGN和TM4SF4首次被报道可能参与EMT过程并预测CRC的预后。我们的研究结果表明，转化生长因子β/Snail与肿瘤坏死因子α/核因子κB的整合通路可能是肿瘤细胞与其微环境联系的主轴，从而导致结直肠癌患者预后不良。
Substantial evidence has shown that epithelial-mesenchymal transition (EMT) plays critical roles in colorectal cancer (CRC) development and prognosis. To uncover the pivotal regulators that function in the cooperative interactions between cancer cells and their microenvironment and consequently affect the EMT process, we carried out a systematic analysis and evaluated prognosis in CRC specimens. Tumor buds and their surrounding stroma were captured using laser microdissection. We used gene expression profiling, bioinformatics analysis and regulatory network construction for molecular selection. The clinical significance of potential biomarkers was investigated. We identified potential EMT biomarkers, including BGN, MMP1, LGALS1, SERPINB5, and TM4SF4, all of which participated in the integrated pathway of TGFβ/Snail with TNFα/NFκB. We also found that BGN, MMP1, LGALS1, SERPINB5 and TM4SF4 were related to CRC patient prognosis. Patients with higher expression of these individual potential biomarkers had poorer prognosis. Among the identified biomarkers, BGN and TM4SF4 are reported, for the first time, to probably be involved in the EMT process and to predict CRC prognosis. Our results strongly suggest that the integrated pathway of TGFβ/Snail with TNFα/NFκB may be the principal axis that links cancer cells to their microenvironment during the EMT process and results in poor prognosis in CRC patients.