Identification of candidate biomarkers correlated with pathogenesis of postoperative peritoneal adhesion by using microarray analysis
Identification of candidate biomarkers correlated with pathogenesis of postoperative peritoneal adhesion by using microarray analysis
复制标题
利用微阵列分析鉴定与术后腹膜粘连发病机制相关的候选生物标志物
DOI：
10.4251/wjgo.v12.i1.54
复制
发表时间：
2020-01-15
影响因子：
3
通讯作者：
Zeng, Li
中科院分区：
文献类型：
--
作者：
Bian, Yao-Yao;Yang, Li-Li;Zeng, Li
### 背景
术后腹膜粘连（PPA）以术后腹痛、女性不孕甚至肠梗阻为特征，一直是备受关注的重大问题。粘连的发生和形成源于复杂的生物学过程。然而，基于微阵列数据图谱的腹膜粘连形成背后的分子机制在很大程度上仍不明确。
### 目的
从分子层面揭示术后腹膜粘连的潜在发病机制。
### 方法
从基因表达综合数据库（Gene Expression Omnibus database）检索基因表达谱用于我们的分析。我们运用生物信息学分析方法确定了一组参与粘连形成的关键基因及相关通路。我们在体内进行了定量聚合酶链反应（PCR）和蛋白质免疫印迹法（western blotting），对结果进行初步验证。
### 结果
腹膜粘连中共发现446个表达改变的基因。我们发现，几个关键基因（如肿瘤坏死因子、白细胞介素1β、白细胞介素6、C-X-C基序趋化因子配体1、C-X-C基序趋化因子配体2）被标记为重要的生物标志物。功能分析表明，这些基因在Toll样受体信号通路中富集。根据京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes）通路及已发表的研究，Toll样受体4（TLR4）、髓样分化初级反应蛋白88（MyD88）和核因子κB（NF-κB）在Toll样信号转导中发挥着重要作用。在此，我们获得了一条涉及术后粘连发病机制的TLR4/MyD88/NF-κB/炎症细胞因子/腹膜粘连的调控证据链。微阵列分析结果通过动物实验得到了验证。这些发现可能会拓展我们对术后腹膜粘连分子机制的理解。
### 结论
TLR4/MyD88/NF-κB/炎症细胞因子/腹膜粘连的调控证据链可能在术后腹膜粘连的发病机制中发挥关键作用。未来还需进一步研究来验证我们的发现。
BACKGROUND Postoperative peritoneal adhesion (PPA), characterized by abdominal pain, female infertility, and even bowel obstruction after surgery, has always been a major concern. The occurrence and formation of adhesion are from complex biological processes. However, the molecular mechanisms underlying the basis of microarray data profile, followed by peritoneal adhesion formation, are largely unknown. AIM To reveal the underlying pathogenesis of PPA at the molecular level. METHODS The gene expression profile was retrieved from the Gene Expression Omnibus database for our analysis. We identified a panel of key genes and related pathways involved in adhesion formation using bioinformatics analysis methods. We performed quantitative PCR and western blotting in vivo to validate the results preliminarily. RESULTS In total, 446 expressed genes were altered in peritoneal adhesion. We found that several hub genes (e.g., tumor necrosis factor, interleukin 1 beta, interleukin 6, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 2) were marked as significant biomarkers. Functional analysis suggested that these genes were enriched in the Toll-like receptor signaling pathway. According to the Kyoto Encyclopedia of Genes and Genomes pathway and published studies, TLR4, myeloid differentiation primary response protein 88 (MyD88), and nuclear factor kappa B (NF-κB) played essential roles in Toll-like signaling transduction. Here, we obtained a regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion involved in the pathogenesis of postoperative adhesion. The results of the microarray analysis were verified by the animal experiments. These findings may extend our understanding of the molecular mechanisms of PPA. CONCLUSION The regulatory evidence chain of TLR4/MyD88/NF-κB/inflammatory cytokines/peritoneal adhesion may play key roles in the pathogenesis of PPA. Future studies are required to validate our findings.