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肺癌和结肠癌患者循环肿瘤细胞的上皮-间质转化分类:在临床实践中的潜在作用。

Epithelial-mesenchymal transition classification of circulating tumor cells in lung and colon cancer patients: potential role in clinical practice.

作者信息

Fang Jinman, Wang Weimin, Fang Jie, Wang Huanzhong, Lin Lin, Li Fei, Sun Qiuyan, Li Feifei, Qi Jian, Sun Xiaojun, Huo Xing-Xing, Wang Shujie, Wang Hongzhi, Hong Bo, Deng Qingmei, Nie Jinfu

机构信息

Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, China.

University of Science and Technology of China, Hefei, China.

出版信息

Transl Cancer Res. 2020 Nov;9(11):6639-6651. doi: 10.21037/tcr-20-2235.

Abstract

BACKGROUND

Tumor cells undergoing epithelial-mesenchymal transition (EMT) display enhanced ability to enter the circulation, thereby being major source of circulating tumor cells (CTCs). In this study, we aimed to better understand the roles of CTC undergoing EMT in monitoring cancer progression.

METHODS

We analyzed gene expression profiling of epithelial and mesenchymal markers in lung or colon tumor samples by mining TCGA database. We detected CTCs and classify their EMT phenotypes of 31 patients with lung or colon cancer by using a CanPatrol CTC-enrichment technique.

RESULTS

The bioinformatic analysis indicated that mesenchymal markers were expressed in a subset of lung tumor samples, and its high expression was associated with poor survival of lung cancer patients. However, in colon cancer, majority of tumor samples expressed hybrid epithelial/mesenchymal markers. CTC analysis with EMT classification showed that the number of CTCs with mesenchymal phenotype was high in lung cancer patients with the advanced stage. Dynamic CTC analysis in a lung cancer patient indicated that CTC with mesenchymal phenotype was effective to monitor tumor progression. In a colon cancer patient, dynamic CTC analysis indicated that CTC with hybrid epithelial/mesenchymal phenotypes was an effective biomarker to guide therapy.

CONCLUSIONS

Encouraging results from this proof-of-concept study show that CTC with mesenchymal phenotype or hybrid epithelial/mesenchymal phenotypes could be a potential biomarker for monitoring tumor progression in lung or colon cancer respectively.

摘要

背景

经历上皮-间质转化(EMT)的肿瘤细胞进入循环的能力增强,因此成为循环肿瘤细胞(CTC)的主要来源。在本研究中,我们旨在更好地了解经历EMT的CTC在监测癌症进展中的作用。

方法

我们通过挖掘TCGA数据库分析了肺或结肠肿瘤样本中上皮和间质标志物的基因表达谱。我们使用CanPatrol CTC富集技术检测了31例肺癌或结肠癌患者的CTC,并对其EMT表型进行分类。

结果

生物信息学分析表明,间质标志物在一部分肺肿瘤样本中表达,其高表达与肺癌患者的不良生存相关。然而,在结肠癌中,大多数肿瘤样本表达混合的上皮/间质标志物。对CTC进行EMT分类分析显示,晚期肺癌患者中间质表型的CTC数量较高。对一名肺癌患者进行的动态CTC分析表明,间质表型的CTC对监测肿瘤进展有效。对一名结肠癌患者进行的动态CTC分析表明,具有混合上皮/间质表型的CTC是指导治疗的有效生物标志物。

结论

这项概念验证研究的令人鼓舞的结果表明,间质表型或混合上皮/间质表型的CTC可能分别是监测肺癌或结肠癌肿瘤进展的潜在生物标志物。

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