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使用二维液相色谱-串联质谱联用iTRAQ技术鉴定结直肠癌中潜在生物标志物双糖链蛋白聚糖和热休克蛋白家族D1成员

Identifying DCN and HSPD1 as Potential Biomarkers in Colon Cancer Using 2D-LC-MS/MS Combined with iTRAQ Technology.

作者信息

Li Guoqing, Li Maoyu, Liang Xujun, Xiao Zhefeng, Zhang Pengfei, Shao Meiying, Peng Fang, Chen Yongheng, Li Yuanyuan, Chen Zhuchu

机构信息

Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, School of Pharmacy and Life Science, University of South China, Hengyang 421001, Hunan, China.

Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China.

出版信息

J Cancer. 2017 Feb 11;8(3):479-489. doi: 10.7150/jca.17192. eCollection 2017.

Abstract

Colon cancer is one of the most common types of gastrointestinal cancers and the fourth cause of cancer death worldwide. To discover novel diagnostic biomarkers for colon cancer and investigate potential mechanisms of oncogenesis, quantitative proteomic approach using iTRAQ-tagging and 2D-LC-MS/MS was performed to characterize proteins alterations in colon cancer and non-neoplastic colonic mucosa (NNCM) using laser capture microdissection-harvested from the two types of tissues, respectively. As a result, 188 DEPs were identified, and the differential expression of two DEPs (DCN and HSPD1) was further verified by Western blotting and immunohistochemistry. KEGG pathway analysis disclosed that the DEPs were related to signaling pathways associated with cancer; furthermore, DCN and HSPD1 are in the relative central hub position among protein-protein interaction subnetwork of the DEPs. The results not only shed light on the mechanism by the DEPs contributed to colonic carcinogenesis, but also showed that DCN and HSPD1 are novel potential biomarkers for the diagnosis of colon cancer.

摘要

结肠癌是最常见的胃肠道癌症类型之一,也是全球癌症死亡的第四大原因。为了发现结肠癌的新型诊断生物标志物并研究潜在的致癌机制,采用iTRAQ标记和二维液相色谱-串联质谱的定量蛋白质组学方法,分别对通过激光捕获显微切割从结肠癌组织和非肿瘤性结肠黏膜(NNCM)中获取的蛋白质变化进行表征。结果,鉴定出188个差异表达蛋白(DEP),并通过蛋白质免疫印迹和免疫组织化学进一步验证了两个DEP(DCN和HSPD1)的差异表达。京都基因与基因组百科全书(KEGG)通路分析表明,这些DEP与癌症相关信号通路有关;此外,DCN和HSPD1在DEP的蛋白质-蛋白质相互作用子网中处于相对中心枢纽位置。这些结果不仅揭示了DEP促进结肠癌发生的机制,还表明DCN和HSPD1是诊断结肠癌的新型潜在生物标志物。

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