Identification of potential up-regulatedhub genes involved in Circulating Tumor Cells (CTCs) incolorectal cancer

Introduction: Colorectal cancer (CRC) is one of the most commoncarcinoma in the world .Circulating Tumor Cells (CTCs)play a key role in cancer progression especially in tumor metastasis.Identification of gene expression differences betweenCTCs and primary tumors can be used as a new type of tumorbiomarkers to improve prediction of clinical outcome in colorectalcancer patients.Materials and Methods: Microarray dataset GSE۸۲۱۹۸ containedCTCs from three metastatic CRC patients and three primarycolon cancer were downloaded from the Gene ExpressionOmnibus (GEO) and Differentially Expressed Genes (DEGs)analyzed using R software.The Gene Ontology (GO) and KyotoEncyclopedia of Genes and Genomes (KEGG) pathway analyseswere conducted based on the Enrichr database.The protein–protein interaction (PPI) network was evaluatedusing the protein interaction database (STRING) and hub genesscreened by Cytoscape. Hub genes were selected for furtheranalysis and their prognostic value and expression patternswere investigated using GEPIA database.Results: Among ۵۰۰۰ DEGs identified between CTC and primarycolon cancer cells, ۸۶۵ genes were upregulated.The overexpressedDEGs were mainly enriched in necroptosis biologicalpathway. The biological processes were mainly involved inpositive regulation of protein localization to centrosome. Themolecular functions and cellular components were significantlyenriched in single-strand DNA endodeoxy ribonuclease activityand recycling endosome respectively.Based on PPI networks, ۱۰ hub genes were selected and foundto be enriched in sphingolipid metabolism pathway.Among the hub genes, the expression levels of PDLIM۴, MICALL۲,NACC۲ and FBXO۳۲ were reduced, whereas those ofTFRC, CERS۲, RAB۷A, WDR۱۲, RHOG and MOSPD۱ wereincreased in CTCs. The survival analysis of hub genes in GEPIAshowed negative correlation of all ۱۰ hub genes with survival.Among those PDLIM۴, MICALL۲, NACC۲, FBXO۳۲,TFRC and WDR۱۲ were statistically significant.Conclusion: These ۱۰ hub genes could serve as novel biomarkersin metastatic colorectal cancer.