CAJ | 학술논문

目的：探讨颈动脉不稳定斑块发生的分子机制。方法从ArrayExpress数据库下载基因表达谱数据E-MTAB-2055。该数据包含24例颈动脉不稳定斑块和24例稳定斑块组织，从中筛选差异基因，并通过富集分析获取与不稳定斑块有关的生物学过程和通路。同时，通过构建差异表达基因的生物网络来寻找与该疾病高度相关的风险模块，并用荧光定量PCR法检测五对不稳定斑块和斑块旁标本，验证风险模块中部分基因的差异表达。结果不稳定斑块中发生显著性差异表达变化的基因共有439个，其中上调基因为232个，下调基因为207个。涉及到的生物学过程和通路大部分与炎症和免疫应答有关。生物网络和模块分析提示CXCR4、VCL和TYROBP可能在不稳定斑块发生发展过程中发挥着重要作用。荧光定量PCR结果显示CXCR4和TYROBP基因表达情况与芯片数据分析结果一致。结论本研究比较完整地揭示了不稳定斑块差异表达谱特征和所涉及的生物学过程和信号通路，其中TYROBP可能是不稳定斑块发生发展进程中新的致病基因。
목적：탐토경동맥불은정반괴발생적분자궤제。방법종ArrayExpress수거고하재기인표체보수거E-MTAB-2055。해수거포함24례경동맥불은정반괴화24례은정반괴조직，종중사선차이기인，병통과부집분석획취여불은정반괴유관적생물학과정화통로。동시，통과구건차이표체기인적생물망락래심조여해질병고도상관적풍험모괴，병용형광정량PCR법검측오대불은정반괴화반괴방표본，험증풍험모괴중부분기인적차이표체。결과불은정반괴중발생현저성차이표체변화적기인공유439개，기중상조기인위232개，하조기인위207개。섭급도적생물학과정화통로대부분여염증화면역응답유관。생물망락화모괴분석제시CXCR4、VCL화TYROBP가능재불은정반괴발생발전과정중발휘착중요작용。형광정량PCR결과현시CXCR4화TYROBP기인표체정황여심편수거분석결과일치。결론본연구비교완정지게시료불은정반괴차이표체보특정화소섭급적생물학과정화신호통로，기중TYROBP가능시불은정반괴발생발전진정중신적치병기인。
Objective To explore the molecular mechanism in the formation of unstable plaques. Methods The cDNA microarray E-MTAB-2055 was downloaded from ArrayExpress database to screen the differentially expressed genes in 24 ruptured plaques against 24 stable plaques. Functional enrichment analysis was conducted to define the biological processes and pathways involved in disease progression. The protein-protein interaction network was constructed to identify the risk modules with close interactions. Five pairs of carotid specimens were used to validate 3 differentially expressed genes of the risk modules by real-time PCR. Results A total of 439 genes showed differential expression in our analysis, including 232 up-regulated and 207 down-regulated genes according to the data filter criteria. Immune-related biological processes and pathways were greatly enriched. The protein-protein interaction network and module analysis suggested that TYROBP, VCL and CXCR4 might play critical roles in the development of unstable plaques, and differential expressions of CXCR4 and TYROBP in carotid plaques were confirmed by real-time PCR. Conclusion Our study shows the differential gene expression profile, potential biological processes and signaling pathways involved in the process of plaque rupture. TYROBP may be a new candidate disease gene in the pathogenesis of unstable plaques.