Identification of key genes involved in the metastasis of clear cell renal cell carcinoma

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common and lethal renal malignant tumor in adults. The aim of the present study was to identify the key genes involved in ccRCC metastasis. Expression profiling data for ccRCC patients with metastasis and without metastasis were obtained from The Cancer Genome Atlas database. The datasets were used to identify differentially expressed genes (DEGs) between the metastasis group and the non-metastasis group using the DESeq2 package. Function enrichment analyses of DEGs were performed. The protein-protein interaction (PPI) network was constructed and analyzed using the Search Tool for the Retrieval of Interacting Genes and Cytoscape for further analysis of the identified hub genes. A total of 472 DEGs were identified, including 247 that were upregulated and 225 that were downregulated in the metastasis group. Gene Ontology enrichment analysis revealed that DEGs were mainly enriched in cell transmembrane movement and mitotic cell cycle process. Kyoto Encyclopedia of Genes Genomes pathway analysis revealed that the DEGs were mainly involved in the ‘cell cycle’ (hsa04110), ‘collecting duct acid secretion’ (hsa04966), ‘complement and coagulation cascades’ (hsa04610) and ‘aldosterone-regulated sodium reabsorption’ (hsa04960) pathways. Using the PPI network, 35 hub genes were identified, and the majority of them were upregulated in ccRCC tissue compared with normal kidney tissue. The expression levels of certain hub genes (CDKN3, TPX2, BUB1B, CDCA8, UBE2C, NDC80, RRM2, NCAPG, NCAPH, PTTG1, FAM64A, ANLN, KIF4A, CEP55, CENPF, KIF20A, ASPM and HJURP) were significantly associated with overall survival and recurrence-free survival in ccRCC. The present study has identified key genes associated with the metastasis of ccRCC.

Identification of key biomarkers and functional pathways in osteosarcomas with lung metastasis: Evidence from bioinformatics analysis

“…Previous studies have prevailingly focused on the relationship between ASPM gene mutations and autosomal recessive primary microcephaly and abnormal neuronal differentiation [44] . Nevertheless, except for its role in normal physiological regulatory functions, recent studies have also found that the upregulation of ASPM promotes the metastasis of tumors, including prostate cancer, endometrial cancer, melanomas, bladder cancer, clear cell renal cell carcinoma [45][46][47][48][49] . Pai et al [50] previously pointed out that overexpression of ASPM has energetically in uence on prostate cancer cell proliferation and invasion, as it could enhance the Wnt-induced βcatenin transcriptional activity through interacting with disheveled-3, which is a cardinal upstream regulator of Wnt signaling.…”

The Genes—Candidates for Prognostic Markers of Metastasis by Expression Level in Clear Cell Renal Cell Cancer

“…Gene expression profiles were studied using microarrays on cultured metastatic RCC (ACHN) and primary RCC (CAKI-2) cell lines, to identify and analyze cancer stem cells [62]. In the works presented here, as well as in the works devoted to the analysis of the expression of individual genes [4,[9][10][11], missing information on the applicability of the revealed differences in expression as markers of metastasis.…”

“…The mechanisms of metastasis are still not well-understood [8]. Currently, some genes associated with the ccRCC metastasis are known [4,[9][10][11], but the possibility of their use as markers is not shown [4]. The identification of such markers could enable personalized approaches to postoperative treatment, as well as contribute to an understanding of the molecular pathways for targeted therapeutic interventions [8,12].…”

A Novel Prognostic Index Based on Alternative Splicing in Papillary Renal Cell Carcinoma

“…In the pathway that genes enriched, "EGFR tyrosine kinase inhibitor resistance" and "platium drug resistance" were involved. EGFR (Wei et al, 2013;Robichaux et al, 2018) and platium (Vaughn et al, 2009;Teo et al, 2017;Pal et al, 2018) have been reported to be involved in the treatment of cancer, and through these enriched genes we may be able to discover specific mechanisms of drug resistance.…”