scholarly journals Identification of 8 feature genes related to clear cell renal cell carcinoma progression based on co-expression analysis

2021 ◽  
Author(s):  
Xiaoxia Yu ◽  
Hua Wu ◽  
Hongmei Wang ◽  
He Dong ◽  
Bihu Gao
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Risk Scores ◽  
Migration And Invasion ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma ◽  
Core Genes

Backgrounds: To screen biomarkers related to clear cell renal cell carcinoma (ccRCC) progression and prognosis. Methods: 1,026 ccRCC-related genes were dug from 494 ccRCC samples in TCGA based on weighted gene co-expression network analysis, and 7 modules were identified. Afterwards, GO and KEGG enrichment analyses were conducted on modules of interest. Genes in these modules were taken as the input to construct a protein-protein interaction network. Thereafter, 30 genes with the highest connectivity were taken as core genes. Univariate Cox regression, LASSO Cox regression and multivariate Cox regression analyses were performed on core genes. Univariate and multivariate Cox regression analyses were performed on patient’s clinical characteristics and risk scores. Results: Stage displayed significantly strong correlations with green module and red module (p<0.001). Genes in modules participated in biological functions including T cell proliferation and regulation of lymphocyte activation. GSEA showed that high- and low-risk groups exhibited significant enrichment differences in pathways related to immunity, cell migration and invasion. Immune infiltration analysis also presented strong correlation between expression of these 8 genes and immune cell infiltration in ccRCC samples. It was displayed that risk score could be an independent factor to assess patient’s prognosis. Conclusion: We determined biomarkers relevant to ccRCC progression, offering candidate targets for ccRCC treatment.

scholarly journals A novel 10 glycolysis-related genes signature could predict overall survival for clear cell renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qianwei Xing ◽  
Tengyue Zeng ◽  
Shouyong Liu ◽  
Hong Cheng ◽  
Limin Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract Background The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Methods Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. Results Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. Conclusions A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival.

scholarly journals High Expression of CDCA7 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma and Its Associations With Immunity

2021 ◽  
Author(s):  
Shouyong Liu ◽  
Yi Wang ◽  
Chenkui Miao ◽  
Qianwei Xing ◽  
Zengjun Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Independent Prognostic Factor ◽  
Gene Set Enrichment Analysis ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract BackgroundCell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive role of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasis on immunity.MethodsThe RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated.ResultsOur results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P<0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P<0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. As for immunity, CDCA7 was significantly associated with tumor mutational burden (TMB), immune checkpoint molecules, tumor microenvironment and immune infiltration.ConclusionsCDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to immunity

scholarly journals A New Survival Model Based on Cholesterol Biosynthesis-Related Genes for Prognostic Prediction in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xiaochen Qi ◽  
Xin Lv ◽  
Xiaoxi Wang ◽  
Zihao Ruan ◽  
Peizhi Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Cholesterol Biosynthesis ◽  
Kidney Tissue ◽  
Survival Model ◽  
Risk Scores ◽  
Cell Renal Cell Carcinoma

In our study, the value of cholesterol biosynthesis is related to clinical analysis in 32 cancer forms in the GSEA database facility. We have a mutation between 25 CBRGs. In The Cancer Genome Atlas database, clear cell renal cell carcinoma (ccRCC, n = 539 ) was upregulated or downregulated in 22 out of 25 cases ( n = 72 ) compared with normal kidney tissue. Then, using LASSO regression analysis, the survival model that is based on nine risk-related CBRGs (CYP51A1, HMGCR, HMGCS1, IDI1, FDFT1, SQLE, ACAT2, FDPS, and NSDHL) is established. ROC curves confirmed the good omen of the new survival mode, and the area under the curve is 0.72 (5 years) and 0.709 (10 years). High SQLE and ACAT2 expression and low NSDHL, FDPS, CYP51A1, FDFT1, HMGCS1, HMGCR, and IDI1 expression were closely related to patients with high-risk renal clear cell carcinoma. Two types of Cox regression, uni- and multivariate, were used to determine risk scores, age, staging, and grade as independent risk factors for prognosis in patients with clear cell renal cell carcinoma. The results showed the prediction model established by 9 selected CBRGs could predict the prognosis more accurately.

scholarly journals High expression of CDCA7 predicts poor prognosis for clear cell renal cell carcinoma and explores its associations with immunity

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shouyong Liu ◽  
Yi Wang ◽  
Chenkui Miao ◽  
Qianwei Xing ◽  
Zengjun Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Division ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Independent Prognostic Factor ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract Background Cell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive roles of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasize its associations with immunity. Methods The RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated. Results Our results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P < 0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P < 0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. Moreover, CDCA7 was significantly related to microsatellite instability (MSI, P < 0.001) and tumor mutational burden (TMB, P < 0.001). As for immunity, CDCA7 was remarkably associated with immune infiltration, tumor microenvironment, immune checkpoint molecules and immune pathways. Conclusions CDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to MSI, TMB, and immunity.

scholarly journals High expression of CDCA7 predicts poor prognosis for clear cell renal cell carcinoma and explores its associations with immunity

2021 ◽  
Author(s):  
Shouyong Liu ◽  
Yi Wang ◽  
Chenkui Miao ◽  
Qianwei Xing ◽  
Zengjun Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Division ◽  
Prognostic Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Independent Prognostic Factor ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract Background: Cell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive roles of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasize its associations with immunity.Methods: The RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated.Results: Our results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P<0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P<0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. Moreover, CDCA7 was significantly related to microsatellite instability (MSI, P<0.001) and tumor mutational burden (TMB, P<0.001). As for immunity, CDCA7 was remarkably associated with immune infiltration, tumor microenvironment, immune checkpoint molecules and immune pathways.Conclusions: CDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to MSI, TMB, and immunity.

scholarly journals Positive feedback regulation of lncRNA PVT1 and HIF2α contributes to clear cell renal cell carcinoma tumorigenesis and metastasis

Oncogene ◽  
2021 ◽  
Author(s):  
Ming-xiao Zhang ◽  
Li-zhen Zhang ◽  
Liang-min Fu ◽  
Hao-hua Yao ◽  
Lei Tan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Positive Feedback ◽  
Renal Cell ◽  
Clear Cell ◽  
Biological Significance ◽  
Specific Inhibitor ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Cell Renal Cell Carcinoma

AbstractLong noncoding RNAs (lncRNAs) have been reported to exert important roles in tumors, including clear cell renal cell carcinoma (ccRCC). PVT1 is an important oncogenic lncRNA which has critical effects on onset and development of various cancers, however, the underlying mechanism of PVT1 functioning in ccRCC remains largely unknown. VHL deficiency-induced HIF2α accumulation is one of the major factors for ccRCC. Here, we identified the potential molecular mechanism of PVT1 in promoting ccRCC development by stabilizing HIF2α. PVT1 was significantly upregulated in ccRCC tissues and high PVT1 expression was associated with poor prognosis of ccRCC patients. Both gain-of-function and loss-of function experiments revealed that PVT1 enhanced ccRCC cells proliferation, migration, and invasion and induced tumor angiogenesis in vitro and in vivo. Mechanistically, PVT1 interacted with HIF2α protein and enhanced its stability by protecting it from ubiquitination-dependent degradation, thereby exerting its biological significance. Meanwhile, HIF2α bound to the enhancer of PVT1 to transactivate its expression. Furthermore, HIF2α specific inhibitor could repress PVT1 expression and its oncogenic functions. Therefore, our study demonstrates that the PVT1/ HIF2α positive feedback loop involves in tumorigenesis and progression of ccRCC, which may be exploited for anticancer therapy.

scholarly journals IgG is involved in the migration and invasion of clear cell renal cell carcinoma

2015 ◽  
Vol 69 (6) ◽  
pp. 497-504 ◽  
Author(s):  
Zhengzuo Sheng ◽  
Yang Liu ◽  
Caipeng Qin ◽  
Zhenhua Liu ◽  
Yeqing Yuan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Cell Lines ◽  
Renal Cell ◽  
Clear Cell ◽  
Migration And Invasion ◽  
Cancer Therapies ◽  
Normal Kidney ◽  
Cell Renal Cell Carcinoma

OBJECTIVE:To investigate if IgG can be expressed in clear cell renal cell carcinoma (cRCC) , and the expression of IgG is involved in the cancer progression. If IgG expression can serve as a potential target in cancer therapies and be used for judging the prognosis.MATERIALS AND METHODS:By immunohistochemistry, we detected IgG in cRCC tissues(75 cRCC tissues and75 adjacent normal kidney tissues). Immunofluorescence and Western blot was used to detect the IgG in cRCC cell lines (786-0, ACHN and CAKI-I). By RT-PCR, the functional transcript of IgG heavy chain was detected. Knockdown of IgG was to analyze the proliferation, migration and invasion ability by CCK8, Transwell and Matrigel and apoptosis in cRCC cell lines.RESULTS:By immunohistochemistry, we found strong staining of IgG in 66 cases of 75 cRCC tissues and 63 cases of 75 adjacent normal kidney tissues. Immunofluorescence and Western blot was found IgG in cRCC cell lines. Knock-down IgG in cRCC cell lines resulted in significant inhibition of cell proliferation, migration and invasion, and the induction of apoptosis of the 786-0 cells. The immunohistochemistry analysis showed that high IgG expression significantly correlated with the poor differentiation and advanced stage of cRCC.CONCLUSION:IgG was over expressed in cRCC and was involved in the proliferation, migration and invasion of cancer cells. IgG expression may serve as a potential target in cancer therapies and could be used for judging the prognosis.

A prognostic nomogram based on competing endogenous RNA network for clear-cell renal cell carcinoma

2020 ◽  
Author(s):  
Yun Peng ◽  
Shangrong Wu ◽  
Zihan Xu ◽  
Dingkun Hou ◽  
Nan Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Rna Sequencing ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Gene Signature ◽  
Expression Data ◽  
Competing Endogenous Rna ◽  
Cell Renal Cell Carcinoma

Abstract Backgroud Clear-cell renal cell carcinoma (ccRCC) is stubborn to traditional chemotherapy and radiation treatment, which makes its clinical management a major challenge. Recently, we have made efforts to understand the etiology of ccRCC. Increasing evidence revealed that the competing endogenous RNA (ceRNA) were involved in the development of various tumor. However, it’s scant for studying on ccRCC, and a comprehensive analysis of prognostic model based on lncRNA-miRNA-mRNA ceRNA regulatory network of ccRCC with large-scale sample size and RNA‐sequencing expression data is still limited. Methods RNA‐sequencing expression data were taken out from GTEx database and TCGA database, A total of 354 samples with ccRCC and 157 normal controlled samples were included in our study. The ccRCC-specific genes were obtained from WGCNA and differential expression analysis. Following, the communication between mRNAs and lncRNAs and target miRNAs were predicted by MiRcode, starBase, miRTarBase, and TargetScan. A gene signature of eight genes was constructed by univariate Cox regression, lasso methods and multivariate Cox regression analysis. Results A total of 2191 mRNAs and 1377 lncRNAs was identified, and a dys-regulated ceRNA network for ccRCC was established using 7 mRNAs, 363 lncRNAs, and 3 miRNAs. Further, a gene signature in cluding 8 genes based on this ceRNA was constructed, meanwhile, a nomogram predicting 1-, 3-, 5-year survival probability containing both clinical characteristics and ccRCC-specific gene signatures was developed. Conclusion It could contribute to a better understanding of ccRCC tumorigenesis mechanism and guide clinicians to make a more accurate treatment decision.

scholarly journals Prognostic Value of DNA Methylation-Driven Genes in Clear Cell Renal Cell Carcinoma: A Study Based on Methylation and Transcriptome Analyses

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Maolin Hu ◽  
Jiangling Xie ◽  
Huiming Hou ◽  
Ming Liu ◽  
Jianye Wang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Renal Cell ◽  
Methylation Level ◽  
Cox Regression ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

Background. Few previous studies have comprehensively explored the level of DNA methylation and gene expression in ccRCC. The purpose of this study was to identify the key clear cell renal cell carcinoma- (ccRCC-) related DNA methylation-driven genes (MDG) and to build a prognostic model based on the level of DNA methylation. Methods. RNA-seq transcriptome data and DNA methylation data were obtained from The Cancer Genome Atlas. Based on the MethylMix algorithm, we obtain ccRCC-related MDG. The univariate and multivariate Cox regression analyses were employed to investigate the correlation between patient overall survival and the methylation level of each MDG. Finally, a prognosis risk score was established based on a linear combination of the regression coefficient derived from the multivariate Cox regression model (β) multiplied with the methylation level of the gene. Results. 19 ccRCC-related MDG were identified. Three MDG (NCKAP1L, EVI2A, and BATF) were further screened and integrated into a prognostic risk score model, risk score=3.710∗methylation level of NCKAP1L+−3.892∗methylation level of EVI2A+−3.907∗methylation level of BATF. The risk model was independent from conventional clinical characteristics as a prognostic factor for ccRCC (HR=1.221, 95% confidence interval: 1.063–1.402, and P=0.005). The joint survival analysis showed that the gene expression and methylation levels of the prognostic genes EVI2A and BATF were significantly related with prognosis. Conclusion. This study provided an important bioinformatics foundation for in-depth studies of ccRCC DNA methylation.

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