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 Epigenetic signature predicts overall survival clear cell renal cell carcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yejinpeng Wang ◽  
Liang Chen ◽  
Lingao Ju ◽  
Kaiyu Qian ◽  
Xinghuan Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

Abstract Background Recently, increasing study have found that DNA methylation plays an important role in tumor, including clear cell renal cell carcinoma (ccRCC). Methods We used the DNA methylation dataset of The Cancer Genome Atlas (TCGA) database to construct a 31-CpG-based signature which could accurately predict the overall survival of ccRCC. Meanwhile, we constructed a nomogram to predict the prognosis of patients with ccRCC. Result Through LASSO Cox regression analysis, we obtained the 31-CpG-based epigenetic signature which were significantly related to the prognosis of ccRCC. According to the epigenetic signature, patients were divided into two groups with high and low risk, and the predictive value of the epigenetic signature was verified by other two sets. In the training set, hazard ratio (HR) = 13.0, 95% confidence interval (CI) 8.0–21.2, P < 0.0001; testing set: HR = 4.1, CI 2.2–7.7, P < 0.0001; entire set: HR = 7.2, CI 4.9–10.6, P < 0.0001, Moreover, combined with clinical indicators, the prediction of 5-year survival of ccRCC reached an AUC of 0.871. Conclusions Our study constructed a 31-CpG-based epigenetic signature that could accurately predicted overall survival of ccRCC and staging progression of ccRCC. At the same time, we constructed a nomogram, which may facilitate the prediction of prognosis for patients with ccRCC.

A robust ferroptosis-related gene signature predicts overall survival in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Li Canxuan ◽  
Long Dan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Risk Groups ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Entire Group ◽  
Cell Renal Cell Carcinoma

Aims: To investigate the prognostic values and potential mechanisms of ferroptosis-related genes in clear cell renal cell carcinoma. Methods: Univariate Cox, least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were employed to identify prognosis-related hub ferroptosis-related genes and establish a prognostic model. Results: The authors established a novel clinical predictive model based on seven hub ferroptosis-related genes in The Cancer Genome Atlas training cohort (n = 374) that was verified in the testing cohort (n = 156) and the entire group (n = 530). Functional analysis indicated that several carcinogenic pathways were enriched. Tumor-infiltrating cells and immunosuppressive molecules were significantly different between the two risk groups. Conclusion: Collectively, the authors successfully constructed a novel ferroptosis-related risk signature that was significantly associated with the prognosis of clear cell renal cell carcinoma.

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 Profiles of overall survival-related gene expression-based risk signature and their prognostic implications in clear cell renal cell carcinoma

2020 ◽  
Vol 40 (9) ◽  
Author(s):  
Zihao He ◽  
Tuo Deng ◽  
Xiaolu Duan ◽  
Guohua Zeng
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Family Member ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Training Set ◽  
Cell Renal Cell Carcinoma ◽  
Validation Set

Abstract The present work aimed to evaluate the prognostic value of overall survival (OS)-related genes in clear cell renal cell carcinoma (ccRCC) and to develop a nomogram for clinical use. Transcriptome data from The Cancer Genome Atlas (TCGA) were collected to screen differentially expressed genes (DEGs) between ccRCC patients with OS &gt; 5 years (149 patients) and those with &lt;1 year (52 patients). In TCGA training set (265 patients), seven DEGs (cytochrome P450 family 3 subfamily A member 7 (CYP3A7), contactin-associated protein family member 5 (CNTNAP5), adenylate cyclase 2 (ADCY2), TOX high mobility group box family member 3 (TOX3), plasminogen (PLG), enamelin (ENAM), and collagen type VII α 1 chain (COL7A1)) were further selected to build a prognostic risk signature by the least absolute shrinkage and selection operator (LASSO) Cox regression model. Survival analysis confirmed that the OS in the high-risk group was dramatically shorter than their low-risk counterparts. Next, univariate and multivariate Cox regression revealed the seven genes-based risk score, age, and Tumor, lymph Node, and Metastasis staging system (TNM) stage were independent prognostic factors to OS, based on which a novel nomogram was constructed and validated in both TCGA validation set (265 patients) and the International Cancer Genome Consortium cohort (ICGC, 84 patients). A decent predictive performance of the nomogram was observed, the C-indices and corresponding 95% confidence intervals of TCGA training set, validation set, and ICGC cohort were 0.78 (0.74–0.82), 0.75 (0.70–0.80), and 0.70 (0.60–0.80), respectively. Moreover, the calibration plots of 3- and 5 years survival probability indicated favorable curve-fitting performance in the above three groups. In conclusion, the proposed seven genes signature-based nomogram is a promising and robust tool for predicting the OS of ccRCC, which may help tailor individualized therapeutic strategies.

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 Identification of a three-m6A related gene risk score model as a potential prognostic biomarker in clear cell renal cell carcinoma

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8827 ◽  
Author(s):  
Yiqiao Zhao ◽  
Zijia Tao ◽  
Xiaonan Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Experimental Studies ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

Background Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent malignancies worldwide, N6-methyladenosine (m6A) has been shown to play important roles in regulating gene expression and phenotypes in both health and disease. Here, our purpose is to construct a m6A-regulrator-based risk score (RS) for prediction of the prognosis of ccRCC. Methods We used clinical and expression data of m6A related genes from The Cancer Genome Atlas (TCGA) dataset and the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression analysis to develop an RS to predict survival of patients with ccRCC, and analyzed correlations between RS and other clinical indicators such as age, grade and stage. Validation of this RS was then engaged in another cohort, E-MTAB-1980 from the ArrayExpress dataset. Finally, we used quantitative real-time PCR to analyze the expression profile of genes consists of the RS. Results A three-gene RS including METTL3, METTL14 and HNRNPA2B1 which can predict overall survival (OS) of ccRCC patients from TCGA. After applying this RS into the validation cohort from Arrayexpress, we found that it successfully reproduced the result; furthermore, the results of PCR validation were in line with our analysis. Conclusion To sum up, our study has identified an RS composed of m6A related genes that may predict the prognosis of ccRCC patients, which might be helpful for future therapeutic strategies. Our results call for further experimental studies for validations.

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 Development and Validation of a Prognostic Gene Signature in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Chuanchuan Zhan ◽  
Zichu Wang ◽  
Chao Xu ◽  
Xiao Huang ◽  
Junzhou Su ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Risk Scores ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC), one of the most common urologic cancer types, has a relatively good prognosis. However, clinical diagnoses are mostly done during the medium or late stages, when mortality and recurrence rates are quite high. Therefore, it is important to perform real-time information tracking and dynamic prognosis analysis for these patients. We downloaded the RNA-seq data and corresponding clinical information of ccRCC from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A total of 3,238 differentially expressed genes were identified between normal and ccRCC tissues. Through a series of Weighted Gene Co-expression Network, overall survival, immunohistochemical and the least absolute shrinkage selection operator (LASSO) analyses, seven prognosis-associated genes (AURKB, FOXM1, PTTG1, TOP2A, TACC3, CCNA2, and MELK) were screened. Their risk score signature was then constructed. Survival analysis showed that high-risk scores exhibited significantly worse overall survival outcomes than low-risk patients. Accuracy of this prognostic signature was confirmed by the receiver operating characteristic curve and was further validated using another cohort. Gene set enrichment analysis showed that some cancer-associated phenotypes were significantly prevalent in the high-risk group. Overall, these findings prove that this risk model can potentially improve individualized diagnostic and therapeutic strategies.

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 Identification of a Novel Epigenetic Signature CHFR as a Potential Prognostic Gene Involved in Metastatic Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiangling Chen ◽  
Jiatian Lin ◽  
Qiaoling Chen ◽  
Ximian Liao ◽  
Tongyu Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Transcription Initiation ◽  
Cox Regression ◽  
Clear Cell ◽  
The Cancer Genome Atlas ◽  
Migration Ability ◽  
Cell Renal Cell Carcinoma ◽  
Expression Levels

Metastasis is the main cause of clear cell renal cell carcinoma (ccRCC) treatment failure, and the key genes involved in ccRCC metastasis remain largely unknown. We analyzed the ccRCC datasets in The Cancer Genome Atlas database, comparing primary and metastatic ccRCC tumor records in search of tumor metastasis–associated genes, and then carried out overall survival, Cox regression, and receiver operating characteristic (ROC) analyses to obtain potential prognostic markers. Comprehensive bioinformatics analysis was performed to verify that the checkpoint with forkhead associated and ring finger domains (CHFR) gene is a reliable candidate oncogene, which is overexpressed in ccRCC metastatic tumor tissue, and that high expression levels of CHFR indicate a poor prognosis. A detailed analysis of the methylation of CHFR in ccRCC tumors showed that three sites within 200 bp of the transcription initiation site were significantly associated with prognosis and that hypomethylation was associated with increased CHFR gene expression levels. Knockdown of CHFR in ccRCC cells inhibited cell proliferation, colony formation, and migration ability. In summary, our findings suggest that the epigenetic signature on CHFR gene is a novel prognostic feature; furthermore, our findings offer theoretical support for the study of metastasis-related genes in ccRCC and provided new insights for the clinical treatment of the disease.

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