Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

Luo, Ting; Chen, Xiaoyi; Zeng, Shufei; Guan, Baozhang; Hu, Bo; Meng, Yong; Liu, Fanna; Wong, Taksui; Lu, Yongpin; Chen, Yun; Hocher, Berthold; Yin, Lianghong

doi:10.3892/ol.2018.8842

Cited by 22 publications

(23 citation statements)

References 53 publications

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“…ENO2 participates in glycolysis and promotes the conversion of b-glycerophosphate to dihydroxyacetone phosphate (39,40). In a previous study, ENO2 was shown to be a pro-survival factor in renal cancer (41). However, to the best of our knowledge, the underlying mechanism of this action has not been clarified.…”

Section: Discussionmentioning

confidence: 94%

Identification of hub genes associated with outcome of clear cell renal cell carcinoma

Wang

et al. 2020

Oncol Lett

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Clear cell renal cell carcinoma (ccRCC) is one of the most common tumor types of the urinary system. Bioinformatics tools have been used to identify new biomarkers of ccRCC and to explore the mechanisms underlying development and progression of ccRCC. The present study analyzed the differentially expressed genes (DEGs) associated with RCC using data obtained from Gene Expression Omnibus datasets and GEO2R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of these DEGs was performed and analyzed using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes to identify the hub genes, defined as the genes with the highest degree of interrelation. Subsequently, differential expression and survival analyses of hub genes was performed using The Cancer Genome Atlas database and Gene Expression Profiling Interactive Analysis (GEPIA) online tool. Using GEO2R, 1,650 DEGs were identified, including 743 upregulated and 907 downregulated genes. GO and KEGG pathway analyses indicated that the upregulated DEGs were primarily involved in blood vessel and vasculature development, whereas downregulated DEGs were primarily involved in organic acid metabolic processes and carboxylic acid metabolic processes. Subsequently, important modules were identified in the PPI network using Cytoscape's Molecular Complex Detection. The 15 most connected hub genes were identified among DEGs, including glycine decarboxylase (GLDC), enolase 2 (ENO2) and topoisomerase II alpha. GEPIA revealed the association between expression levels of hub genes and survival. Specifically, GLDC and ENO2 were associated with the prognosis of patients with RCC and thus, the effects of GLDC and ENO2 involvement in renal cancer were investigated in vitro. GLDC and ENO2 affected the proliferation and apoptosis of renal cancer cells. These hub genes may reveal a new mechanism underlying development or progression of RCC and identify new markers for its diagnosis and prognosis.

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Section: Discussionmentioning

confidence: 94%

Identification of hub genes associated with outcome of clear cell renal cell carcinoma

Wang

et al. 2020

Oncol Lett

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“…Recent evidence from a multivariate analysis showed that high ENO2 expression was an independent prognostic factor for acute lymphoblastic leukemia patients [37]. Another recent study concluded that high ENO2 expression was associated with poor overall survival in ccRCC patients [38]. However, there are no reports describing the relationship between ENO2, CDH6 and LTF in RCC.…”

Section: Discussionmentioning

confidence: 99%

“…Upregulation of LRP1 has been reported in various human diseases, and LRP1 plays a critical role in the regulation of many cellular processes, including survival, cell proliferation, motility, and differentiation [39]. Previous studies have demonstrated that tissue-type plasminogen activator binds to LRP1 and activates extracellular signal-regulated kinases (Erk)1/2 to stimulate matrix metalloproteinase (MMP)-9 production and induce the EMT of kidney cells [38]. Additionally, LRP1 has been shown to be upregulated in various cancers and promotes cancer cell invasion, migration and tumor progression through the activation of focal adhesion kinase (FAK), Akt and Erk1/2 pathways [40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Lactotransferrin Downregulation Drives the Metastatic Progression in Clear Cell Renal Cell Carcinoma

Chiu

Hsu

Chang

et al. 2020

Cancers

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Clear cell renal cell carcinoma (ccRCC) is the main type of RCC, which is the most common type of malignant kidney tumor in adults. A subpopulation (>30%) of ccRCC patients develop metastasis; however, the molecular mechanism remains largely unknown. Here, we found that LTF, the gene encoding lactotransferrin, is dramatically downregulated in primary tumors compared to normal tissues derived from ccRCC patients deposited in The Cancer Genome Atlas (TCGA) database and is a favorable prognostic marker. Moreover, LTF downregulation appears to be more dominant in metastatic ccRCC. LTF overexpression suppresses migration ability in A498 ccRCC cells with high metastatic potential, whereas LTF knockdown fosters cellular migration in poorly metastatic ccRCC cells. Gene set enrichment analysis demonstrated that LTF expression inversely correlates with the progression of epithelial-mesenchymal transition (EMT) in ccRCC, which was further confirmed by RT-PCR experiments. Therapeutically, the administration of recombinant LTF protein significantly suppresses the cell migration ability and lung metastatic potential of ACHN cells, as well as LTF-silenced A498 cells. The gene knockdown of lipoprotein receptor-related protein 1 (LRP1) robustly blocked recombinant LTF protein-induced inhibition of cellular migration and gene expression of EMT markers in ACHN cells. LTF downregulation and LRP1 upregulation combined predicted a poor overall survival rate in ccRCC patients compared to that with either factor alone. Our findings uncover a new mechanism by which LTF may interact with LRP1 to inhibit metastatic progression in ccRCC and also reveal the therapeutic value of recombinant LTF protein in treating metastatic ccRCC.

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“…However, histological classification is limited in its ability to predict patient outcome, even in clear cell RCC (ccRCC) 4,5 . In that regard, biological markers that predict patient outcome in ccRCC are available 6–8 . Recently, somatic copy number alterations (SCNAs) have been used to predict tumor aggressiveness in ccRCC 9,10 .…”

Section: Introductionmentioning

confidence: 99%

“…4,5 In that regard, biological markers that predict patient outcome in ccRCC are available. [6][7][8] Recently, somatic copy number alterations (SCNAs) have been used to predict tumor aggressiveness in ccRCC. 9,10 Several studies have demonstrated that the presence of multiple SCNAs is associated with overall patient survival, tumor stage, and development of metastasis.…”

mentioning

confidence: 99%

Comprehensive analysis of somatic copy number alterations in clear cell renal cell carcinoma

Tsuyukubo

Ishida

Osakabe

et al. 2020

Molecular Carcinogenesis

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Somatic copy number alterations (SCNAs) are important biological characteristics that can identify genome‐wide alterations in renal cell carcinoma (RCC). Recent studies have shown that SCNAs have potential value for determining the prognosis of RCC. We examined SCNAs using the Affymetrix platform to analyze samples from 59 patients with clear cell RCCs (ccRCCs) including first cohort (30 cases) and second cohort (validation cohort, 29 cases). We stratified SCNAs in the ccRCCs using a hierarchical cluster analysis based on SCNA types, including gain, loss of heterozygosity (LOH), copy neutral LOH, mosaic, and mixed types. In this way, the examined two cohorts were categorized into two subgroups (1 and 2). Although the frequency of mixed type was higher in subgroup 1 than in subgroup 2 in the two cohorts, the association did not reach statistical significance. There was a significant difference in the frequency of metachronous metastasis between subgroups 1 and 2 (subgroup 2 > 1). In addition, subgroup 2 was retained in multivariate analysis of both cohorts. We examined whether there were specific alleles differing between subgroups 1 and 2 in both cohorts. We found that there was indeed a statistically significant difference in the 3p mixed types. Among the 3p mixed type, we found that 3p24.3 mixed type was inversely correlated with the presence of metachronous metastasis in ccRCC. The association was also retained in multivariate analysis in second cohort. We suggest that the 3p24.3 mixed type may be a novel marker to predict a favorable prognosis in ccRCC.

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Bioinformatic identification of key genes and analysis of prognostic values in clear cell renal cell carcinoma

Cited by 22 publications

References 53 publications

Identification of hub genes associated with outcome of clear cell renal cell carcinoma

Identification of hub genes associated with outcome of clear cell renal cell carcinoma

Lactotransferrin Downregulation Drives the Metastatic Progression in Clear Cell Renal Cell Carcinoma

Comprehensive analysis of somatic copy number alterations in clear cell renal cell carcinoma

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