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.

Background: Clear cell renal cell carcinoma (ccRCC) is one of the common malignant tumors worldwide.There is still a lack of effective diagnostic and therapeutic targets for the recurrence and metastasis of ccRCC. In this study, we sought to identify effective diagnostic and therapeutic targets for ccRCC recurrence and metastasis.Methods: Gene Expression Omnibus (GEO) dataset was used to obtain differentially expressed genes (DEGs) between primary and metastasis ccRCC. We used The Cancer Genome Atlas (TCGA), GeneMANIA, cBioPortal, MethSurv, and TIMER to analyze the expression differences, mutation status, prognostic value, molecular function, and immune infiltration of hub genes in renal cell carcinoma (RCC).Results: We obtained a total of 35 different gene lists. Six collagen family members were identified as hub genes. The expression level of collagen family members was closely related to ccRCC. Moreover, differences in the expression levels of collagen family members were closely related to the stage and prognosis of ccRCC.Members of the collagen family were responsible for more than 15% of the genetic alterations in ccRCC and are involved in multiple signaling pathways. The expression level of collagen family members was closely related to the infiltration of tumor-associated immune cells. Univariate and multivariate Cox regression identified the prognosis-related genes: COL5A1.Conclusions: Our study implied that members of the collagen family may serve as a biomarker for ccRCC metastasis and prognosis.

Background Clear cell renal cell carcinoma(ccRCC) is a frequently occurring malignant tumor of the urinary system. Despite extensive research, the regulatory mechanisms underlying the pathogenesis and progression of ccRCC remain largely unknown. Methods We downloaded 5 ccRCC expression profiles from the Gene Expression Omnibus (GEO) database and obtained the list of differentially expressed genes (DEGs). Using String and Cytoscape tools, we determined the hub genes of ccRCC, and then analyzed their relationship with ccRCC patient survival. Ultimately, we identified SERPINE1 as a prognostic factor in ccRCC. Meanwhile, we confirmed the role of SERPINE1 in 786-O cells by cell transfection and in vitro experiments. Results Our analysis yielded a total of 258 differentially expressed genes, comprising 105 down-regulated genes and 153 up-regulated genes. Survival analysis of SERPINE1 expression in The Cancer Genome Atlas (TCGA) confirmed its association with the increase of tumor grade, lymph node metastasis, and tumor stage, as well as with shorter survival. Furthermore, we found that SERPINE1 expression levels were associated with CD8 + T cells, CD4 + T cells, B cells, macrophages, neutrophils, and dendritic cells. Cell experiments showed that knockdown SERPINE1 expression could inhibit the proliferation, migration and invasion of ccRCC cells. Among the co-expressed genes with the highest correlation, ITGA5, SLC2A3, SLC2A14, SHC1, CEBPB, and ADA were overexpressed and associated with shorter overall survival (OS) in ccRCC. Conclusions In this study, we identified hub genes that are strongly related to ccRCC, and highlights the potential utility of overexpressed SERPINE1 and its co-expressed genes could be used as prognostic and diagnostic biomarkers in ccRCC.

Background The most common type of renal cell carcinoma is clear cell renal cell carcinoma (ccRCC), which has a poor prognosis. In addition to regulating tumor cells' growth and metabolism, cuproptosis can also affect patients' prognosis. However, the function of cuproptosis-related genes(CRGs) in ccRCC remains unclear. Methods Comprehensive bioinformatics analysis was used to evaluate CRGs expression level, prognostic value and relationship with tumor immune infiltration. Furthermore, we constructed prognostic gene models and ceRNA networks based on bioinformatics analysis. Results In ccRCC, we found a total of 16 CRGs up-regulation or down-regulation. We also focused on the mutation of CRGs in ccRCC. Based on prognosis analysis, these genes were associated with ccRCC prognosis. We subsequently constructed a prognostic CRGs model to predict the prognosis of ccRCC patients. Immunocorrelation studies revealed the correlation between CRGs and tumor immune infiltration. The lncRNA OIP5-AS1/miR-222-3p/DBT regulatory axis was constructed in ccRCC. We also verified the expression of DBT and lncRNA OIP5-AS1 in ccRCC cell lines via the qRT-PCR method. Conclusions Through comprehensive bioinformatics analysis, we analyzed the expression and prognostic value of CRGs in ccRCC, and identified the prognostic CRGs signature of ccRCC patients, including NLRP3, FDX1, LIPT2, GLS, CDKN2A, DBT and GCSH. Our follow-up study also found an lncRNA OIP5-AS1/ Mir-222-3p /DBT regulatory axis, which may explain the internal mechanism of CRGs involved in regulating the progression of ccRCC.