School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 West Fifth Road, Xi'an, 710000, China.
Sci Rep. 2023 Apr 28;13(1):6982. doi: 10.1038/s41598-023-34317-2.
Circulating tumor cells (CTCs) play a key role in tumor metastasis. CTCs have altered gene expression and can survive in the bloodstream. Finding the key genes whose expression are altered in CTCs could help explain the mechanism of tumor metastasis. We searched for genes differentially expressed in CTCs by analyzing four CTCs and primary tumor gene expression datasets in the GEO database. Key genes of clear cell renal cell carcinoma (ccRCC) CTCs were identified. The correlation between key genes and the immune microenvironment of ccRCC was explored. Finally, the CTCs cell model of ccRCC was constructed by in vivo screening method, and the expression of key genes was detected at the cell and tissue levels. A total of 771 DEGs were obtained. Gene enrichment analysis showed that DEGs of CTCs were mainly involved in the regulation of the tumor immune process and tumor cell apoptosis. Finally, we found 2 key genes, MMP9 and TYROBP in ccRCC CTCs. The high expression of these 2 genes predicted a poor prognosis of ccRCC, and the expression levels of these 2 genes were significantly increased in CTCs and ccRCC tissues. Our study suggested that genetic alterations in CTCs contribute to the ability of CTCs to survive in the blood by adapting to the tumor microenvironment. MMP9 and TYROBP are potential therapeutic and prognostic targets for ccRCC.
循环肿瘤细胞（CTCs）在肿瘤转移中起着关键作用。CTCs 改变了基因表达，可以在血液中存活。寻找 CTCs 中表达改变的关键基因，可以帮助解释肿瘤转移的机制。我们通过分析 GEO 数据库中的四个 CTC 和原发性肿瘤基因表达数据集，寻找 CTCs 中差异表达的基因。鉴定出透明细胞肾细胞癌（ccRCC）CTCs 的关键基因。探讨关键基因与 ccRCC 免疫微环境的相关性。最后，通过体内筛选方法构建 ccRCC 的 CTCs 细胞模型，检测关键基因在细胞和组织水平上的表达。共获得 771 个差异表达基因。基因富集分析表明，CTCs 的差异表达基因主要参与肿瘤免疫过程和肿瘤细胞凋亡的调节。最后，我们在 ccRCC CTCs 中发现了 2 个关键基因 MMP9 和 TYROBP。这 2 个基因的高表达预示着 ccRCC 的预后不良，而且这 2 个基因在 CTCs 和 ccRCC 组织中的表达水平显著升高。我们的研究表明，CTCs 的遗传改变通过适应肿瘤微环境，有助于 CTCs 在血液中存活的能力。MMP9 和 TYROBP 是 ccRCC 的潜在治疗和预后靶点。
