Identification of key genes and functions of circulating tumor cells in multiple cancers through bioinformatic analysis

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RESEARCH ARTICLE

Open Access

Identification of key genes and functions of circulating tumor cells in multiple cancers through bioinformatic analysis Yibing Guan1,2†, Fangshi Xu1,2†, Yiyuan Wang3†, Juanhua Tian1,2, Ziyan Wan1,2, Zhenlong Wang1 and Tie Chong1*

Abstract Background: Circulating tumor cells (CTCs) play a key role in cancer progression, especially metastasis, due to the rarity and heterogeneity of CTCs, fewer researches have been conducted on them at the molecular level. However, through the Gene Expression Omnibus (GEO) database, this kind of minority researches can be well integrated, the gene expression differences between CTCs and primary tumors can be identified, and molecular targets for CTCs can be found. Methods: We analyzed 7 sets of gene chips (GSE82198, GSE99394, GSE31023, GSE65505, GSE67982, GSE76250, GSE50746) obtained by GEO. Analysis of differentially expressed genes (DEGs) between CTCs and corresponding primary tumors by NetworkAnalyst. Metascape tool for Gene Ontology (GO) / Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differential genes and visual display. Cytoscape performs protein-protein interaction (PPI) analysis and obtains the hub genes. Renal cancer patients’ clinical specimens to verify the correctness of enrichment results. Prognostic analysis of hub genes in kidney cancer patients using the Kaplan–Meier plotter survival analysis tool. Results: We obtained a total of 589 DEGs. The GO / KEGG enrichment results indicate that the DEGs are mainly concentrated in cell adhesion, epithelial-mesenchymal transition (EMT), and apoptosis. Renal cancer clinical specimens suggest that CTCs have epithelial and mesenchymal types. At the same time, PSMC2 can be used as a poor prognostic indicator for renal cancer patients. Conclusions: In summary, our study suggests that compared with primary tumors, CTCs mainly change cell adhesion, EMT, and apoptosis. PSMC2 can be used as a poor prognostic factor. Keywords: Hub genes, Expression profiling data, Cancer, PSMC2, EMT

Background Circulating tumor cells, as cells detached from solid tumors and entering the circulating blood are a new type of tumor biomarker with real-time detection and minimally invasive characteristics [1]. At the same time, CTCs play an important role in tumor progression, especially in the formation of metastases [2]. CTCs have the characteristics * Correspondence: [email protected] † Yibing Guan, Fangshi Xu and Yiyuan Wang contributed equally to this work. 1 Department of Urology, the Second Affiliated Hospital, School of Medicine, Xi’an Jiaotong University, No 157 Xiwu Road, Xi’an 710004, Shaan Xi Province, China Full list of author information is available at the end of the article

of rarity and heterogeneity, which once restricted the researches of CTCs [3]. Nowadays, with the development of technology, not only can CTCs be captured and enriched, but also they can be identified at the molecular level, which greatly improves the clinical application value of CTCs, and provides potential possible