Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma

Shi, Shen-Nan; Qin, Xia; Wang, Shuo; Wang, Wenfu; Zhu, Yao; Lin, Yu; Zhang, Zhou; Shi, Benkang; Liu, Xigao

doi:10.18632/aging.103192

Cited by 5 publications

(5 citation statements)

References 51 publications

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“…After construction of protein-protein interaction network of DEGs, we used CytoHubba to identify the hub genes with degree > 10 and further screened the hub genes to obtain candidate genes related with the prognoses of ccRCC by synthesizing the results of UALCAN, GEPIA and HPA. The results showed that TIMP1, PCK1, HMGCS2, G6PC, FBP1, ACAA1, HADH, HAO2, TGFBI, RRM2 and SUCLG1 are of prognostic signi cance in ccRCC patients, which were consistent with results of previous researches [33][34][35][36][37]. Whereafter, we veri ed the mRNA and protein expression of these genes in different ways, thus obtained three target genes, namely PCK1, HMGCS2 and RRM2.…”

Section: Rrm2 Expression Was Correlated With Immune In Ltration and Immunological Checkpoint In Ccrccsupporting

confidence: 88%

Identification of Biomarkers for Prognosis and Immunotherapy in Clear Cell Renal Cell Carcinoma

Yu¹,

Lü²,

Gao³

et al. 2021

Preprint

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Background: Clear cell renal cell carcinoma (ccRCC) is the dominating subtype of renal cancer with high malignancy and poor prognosis, accounts for the majority of kidney cancer deaths. We conducted this research to identify novel potential biomarkers for the prognosis and immunotherapy of ccRCC patients. We screened out differentially expressed genes (DEGs) between ccRCC tissues and adjacent normal tissues with 4 microarray series from GEO database and took function analysis of DEGs with GO and KEGG pathway. Then, we constructed PPI network and identified target genes with prognostic value in ccRCC, performed immunological correlation analysis of the candidate genes to seek potential biomarkers of immunotherapy in ccRCC. Results: In total, 159 up-regulated genes and 223 down-regulated genes were screened out and 11 genes including TIMP1, PCK1, HMGCS2, G6PC, FBP1, ACAA1, HADH, HAO2, TGFBI, RRM2 and SUCLG1 were found to be associated with prognoses of ccRCC patients. After further screening and verification of the mRNA and protein expression, down-regulation of PCK1, HMGCS2, and up-regulation of RRM2 were significantly correlated with poorer prognoses both in overall survival and disease free survival in ccRCC. Further immunological correlation analysis showed RRM2 expression was correlated with immune infiltration and immunological checkpoint in ccRCC.Conclusion: We identified PCK1, HMGCS2 and RRM2 as potential markers for the prognosis of ccRCC patients with bioinformatic analyses. RRM2 may plays an important role in the oncogenicity of ccRCC and is a potential target for immunotherapy of ccRCC patients.

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Section: Rrm2 Expression Was Correlated With Immune In Ltration and Immunological Checkpoint In Ccrccsupporting

confidence: 88%

Identification of Biomarkers for Prognosis and Immunotherapy in Clear Cell Renal Cell Carcinoma

Yu¹,

Lü²,

Gao³

et al. 2021

Preprint

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“…The analysis of GO processes associated with the genes whose levels of expression are not altered during tumor progression ( HIG2 , INHBB , TYROBP , STC2 , CXCR4 , NNMT , FN1 , PFKP , SLC16A3 , C1QA , and CD36 ) indicates that these genes are activated in the initial phase, and maintained at all stages of development of ccRCC metabolic and inflammatory processes and positive regulation of the multicellular organismal process. These functional features of ccRCC have been noted in previous studies ( 56 – 58 ); however, we identified their early onset and its preservation at all stages of tumor development, which was not previously described.…”

Section: Discussionsupporting

confidence: 51%

The Choice of Candidates in Survival Markers Based on Coordinated Gene Expression in Renal Cancer

et al. 2021

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We aimed to identify and investigate genes that are essential for the development of clear cell renal cell carcinoma (ccRCC) and sought to shed light on the mechanisms of its progression and create prognostic markers for the disease. We used real-time PCR to study the expression of 20 genes that were preliminarily selected based on their differential expression in ccRCC, in 68 paired tumor/normal samples. Upon ccRCC progression, seven genes that showed an initial increase in expression showed decreased expression. The genes whose expression levels did not significantly change during progression were associated mainly with metabolic and inflammatory processes. The first group included CA9, NDUFA4L2, EGLN3, BHLHE41, VWF, IGFBP3, and ANGPTL4, whose expression levels were coordinately decreased during tumor progression. This expression coordination and gene function is related to the needs of tumor development at different stages. Specifically, the high correlation coefficient of EGLN3 and NDUFA4L2 expression may indicate the importance of the coordinated regulation of glycolysis and mitochondrial metabolism. A panel of CA9, EGLN3, BHLHE41, and VWF enabled the prediction of survival for more than 3.5 years in patients with ccRCC, with a probability close to 90%. Therefore, a coordinated change in the expression of a gene group during ccRCC progression was detected, and a new panel of markers for individual survival prognosis was identified.

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“…The Cancer Genome Atlas (TCGA) database ( https://tcga-data.nci.nih.gov/tcga/ ) was used to acquire publicly available messenger RNA (mRNA) profiles and corresponding clinicopathological data from 539 ccRCC tissues and 72 adjacent normal samples, Information recorded included: sex; race; laterality; tumor, node classification, and metastasis classification; tumor, node metastasis (TNM) stage; histologic grade; tumor status; relapse; and vital status. Differentially expressed genes (DEGs) were identified from TCGA database and GEO datasets ( http://www.ncbi.nlm.nih.gov/geo/ ) (including GSE15641 [ 25 ], GSE36895 [ 26 ] and GSE40435 [ 27 ], as well as GSE105261 [ 28 ]) through the “DEseq2” package and via the “Limma” package, respectively. The thresholds were |log2-fold change (FC)| >2.0 and false discovery rate (FDR) <0.01 [ 29 ].…”

Section: Methodsmentioning

confidence: 99%

Overexpression of PKMYT1 Facilitates Tumor Development and Is Correlated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

2020

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Background Protein kinase membrane-associated tyrosine/threonine ( PKMYT1 ) has been found in many tumors, but its association with clear cell renal cell carcinoma (ccRCC) remains unclear. Material/Methods PKMYT1 expression in ccRCC was examined in the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and Tumor Immune Estimation Resource databases. The correlation between PKMYT1 expression and clinicopathological parameters was explored via the chi-square test. Receiver operating characteristic curves were used to estimate the diagnostic performance of PKMYT1 . Kaplan-Meier curves, a Cox model, nomogram, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA) were used to evaluate the prognostic value and clinical utility of PKMYT1 . Genes coexpressed with PKMYT1 in ccRCC were identified based on TCGA, the gene expression profiling interactive, and cBioPortal. Gene Set Enrichment Analysis revealed biological pathways associated with PKMYT1 in ccRCC. Results Weighted gene coexpression network analysis identified PKMYT1 as one of the genes most significantly correlated with progression of histological grade. PKMYT1 was significantly upregulated in ccRCC compared with normal tissue (P<0.001), with a trend toward differentiating between individuals with ccRCC and those who were healthy (area under the curve=0.942). High PKMYT1 expression was correlated with unsatisfactory survival (hazard ratio=1.67, P=0.001), indicating that it is a risk factor for ccRCC. A nomogram incorporating PKMYT1 level was created and showed a clinical net benefit. PKMYT1 was strongly positively correlated with the anti-silencing function of 1B histone chaperone ( ASF1B ) gene in ccRCC. Conclusions PKMYT1 is upregulated in ccRCC and its presence indicates poor prognosis, making it a potential therapeutic target for ccRCC.

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Identification of potential novel differentially-expressed genes and their role in invasion and migration in renal cell carcinoma

Cited by 5 publications

References 51 publications

Identification of Biomarkers for Prognosis and Immunotherapy in Clear Cell Renal Cell Carcinoma

Identification of Biomarkers for Prognosis and Immunotherapy in Clear Cell Renal Cell Carcinoma

The Choice of Candidates in Survival Markers Based on Coordinated Gene Expression in Renal Cancer

Overexpression of PKMYT1 Facilitates Tumor Development and Is Correlated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

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