Cartilage oligomeric matrix protein is a prognostic factor and biomarker of colon cancer and promotes cell proliferation by activating the Akt pathway
Cartilage oligomeric matrix protein is a prognostic factor and biomarker of colon cancer and promotes cell proliferation by activating the Akt pathway
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软骨寡聚基质蛋白是结肠癌的预后因素和生物标志物，通过激活 Akt 通路促进细胞增殖
DOI：
10.1007/s00432-018-2626-4
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发表时间：
2018-06-01
影响因子：
3.6
通讯作者：
Peng, Zhi-hai
中科院分区：
文献类型：
--
作者：
Liu, Ting-ting;Liu, Xi-sheng;Peng, Zhi-hai
目的软骨寡聚基质蛋白（COMP）在肿瘤发生中起重要作用。我们试图澄清COMP在结肠cancer.MethodsWe的作用研究从癌症基因组图谱（TCGA）数据集的基因表达数据。组织微阵列（TMA）含有配对样本从253例结肠癌患者进行免疫染色。用ELISA法检测结肠癌患者和健康献血员血清中COMP水平。我们使用CRISPR/Cas9系统建立了COMP敲除细胞，使用慢病毒载体建立了COMP过表达细胞，使用细胞计数试剂盒-8（CCK 8）、集落形成、细胞凋亡检测试剂盒检测COMP对结肠癌细胞的影响，结果癌组织中COMP的表达水平明显高于癌旁组织，癌旁组织中COMP的表达水平明显高于癌旁组织，癌旁组织中COMP的表达水平明显高于癌旁组织正常组织此外，COMP高表达与结肠癌患者的不良预后相关。术前结肠癌患者血清中COMP水平远高于健康供体，结肠切除术后显著降低。不含COMP的结肠癌细胞在增殖能力、集落形成能力、抵抗5-氟尿嘧啶诱导的细胞凋亡的能力和小鼠异种移植瘤的生长方面是有缺陷的。在COMP过表达的细胞中观察到相反的结果。结论COMP可能是一种新的结肠癌预后指标和生物标志物，也可能是一种潜在的治疗靶点。
PurposeRecent studies have determined that cartilage oligomeric matrix protein (COMP) plays a vital role in carcinogenesis. We sought to clarify the role of COMP in colon cancer.MethodsWe investigated gene expression data from The Cancer Genome Atlas (TCGA) dataset. Tissue microarrays (TMA) containing paired samples from 253 patients with colon cancer were subjected to immunostaining. COMP levels in serum of colon cancer patients and healthy donors were measured with ELISA. We established COMP-knockout cells using the CRISPR/Cas9 system and COMP-overexpressing cells using lentiviral vectors to detect the effects of COMP on colon cancer cells using Cell Counting Kit-8 (CCK8), colony formation, apoptosis detection kit, and tumorigenesis assays in nude mice.ResultsThe analysis of TCGA dataset and the results of the TMA suggested that COMP expression levels were significantly higher in cancer tissues than in adjacent normal tissues. Moreover, high COMP expression was correlated with the poor outcome of colon cancer patients. COMP levels in the sera of preoperative patients with colon cancer were much higher than those in healthy donors and were significantly reduced after colectomy. Colon cancer cells without COMP were defective with respect to the ability to proliferate, colony formation, the ability to resist 5-Fluorouracil-induced apoptosis and the growth of xenograft tumors in mice. Contrasting results were observed in COMP overexpressed cells. COMP promoted colon cancer cell proliferation partially through the activation of PI3K/ Akt/ mTOR/ p70S6K pathway.ConclusionsCOMP may be a novel prognostic indicator and biomarker and also a potential therapeutic target for colon cancer.