应用生物信息学筛选大肠癌转移相关小分子化合物  

Screening the metastasis-related small molecule compounds of colorectal cancer by bioinformatics methods

作　　者：齐鲁[1] 丁彦青[1,2] 

机构地区：[1]南方医科大学基础医学院病理学系,广东广州510515 [2]南方医科大学南方医院病理科,广东广州510515

出　　处：《西安交通大学学报（医学版）》2013年第6期797-802,共6页Journal of Xi’an Jiaotong University（Medical Sciences）

摘　　要：目的筛选并分析与大肠癌转移相关的小分子化合物。方法首先通过大肠癌早期转移组织表达谱数据与正常大肠组织数据进行统计学比较,筛选出差异表达基因,再通过差异表达基因与小分子的对应模式筛选出与大肠癌早期转移相关的小分子化合物,最后通过分析小分子化合物的靶蛋白在大肠癌疾病类中的富集情况,筛选靶蛋白中与大肠癌相关的部分靶蛋白,结合大肠癌表达谱的表达情况以及小分子化合物与靶蛋白的结合情况筛选最相关的靶蛋白并进行网络调控情况分析。结果通过小分子化合物的富集分析,tanespimycin得分最高,并且其靶蛋白在大肠癌疾病类中富集程度最高,说明tanespimycin与大肠癌关系密切;综合表达情况以及分子结合强度,明确与大肠癌相关的靶蛋白CHEK1、AURKA、GSTP1、NQO1可能为tanespimycin对大肠癌转移治疗作用中的关键蛋白,并且这4个靶蛋白构成的网络参与了与药物代谢相关的生物进程,进一步说明其与tanespimycin的关系。结论 tanespimycin可能是能够抑制大肠癌早期转移的小分子化合物,其主要通过与其相互作用的靶蛋白CHEK1、AURKA、GSTP1、NQO1调控大肠癌转移相关的信号网络。Objective To screen and analyze small molecule therapeutic compounds associated with colorectal cancer metastasis. Methods First statistical comparison was made for the expression profile data of early metastasizing colorectal cancer tissues with the data of normal colorectum tissues to screen the differentially expressed genes. Then the matching patterns between differentially expressed genes and the small molecules were used to screen small molecule therapeutic tanespimycin compounds associated with early colorectal cancer metastasis. Last, the enrichment status of the small molecule therapeutic compounds target protein were analyzed to screen the colorectal cancer-related target protein. We combined the colorectal cancer expression profile and the bond strength between small molecule compounds and the target protein to screen the most relevant target protein and build a regulatory network. Results By the small molecule compounds enrichment analysis, tanespimycin had the highest score, the target protein of tanespimycin had the highest score of enrichment in colorectal cancer. It indicated that tanespimycin was closely related to colorectal cancer. By synthesizing the expression profile and the molecular bonding strength, we found that the colorectal cancer-related target proteins named CHEK1, AURKA, GSTP1 and NQO1 might be the key proteins of tanespimycin therapy that inhibited the metastasis of colorectal cancer. The regulatory network was built by the four target proteins participating in the biological process of drug metabolism. That further explained the relationship between the four proteins and tanespimycin. Conclusion Tanespimycin may be the small molecule therapeutic compound that can inhibit early metastasis of colorectal cancer by interacting with CHEK1, AURKA, GSTP1 and NQO1 to regulate the signaling network.

关 键 词：差异表达 大肠癌 转移 tanespimycin生物信息学 基因 靶蛋白 

分 类 号：R735.35[医药卫生—肿瘤]