scholarly journals Identification And Validation Of A Hypoxia ‑ Related Prognostic Signature In Clear Cell Renal Cell Carcinoma Patients

2020 ◽  
Author(s):  
Zhengtian Li ◽  
Lingling Jiang ◽  
Rong Zhao ◽  
Wenkang Yang ◽  
Chan Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Risk Factor ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Independent Risk Factor ◽  
Clear Cell ◽  
External Validation ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Genetic Signatures

Abstract Background: Increasing evidence has shown that hypoxia is closely related to the development, progression and prognosis of clear cell renal cell carcinoma (ccRCC). Nevertheless, reliable prognostic signatures based on hypoxia have not been well-established. This study aimed to construct an optimized prognosis nomogram based on hypoxia-related genetic signatures for patients with ccRCC.Method: We accessed hallmark gene sets of hypoxia, including 200 genes, and an original RNA seq dataset of ccRCC cases with integrated clinical information obtained by mining the Molecular Signatures Database, the TCGA database and the ICGC database. Univariate Cox regression analysis and multivariate Cox proportional hazards regression were performed to identify prognostic hypoxia-related genetic signatures and further generate RiskScore, a new independent prognosis predictor for optimizing prognosis models. External validation of the optimized prognosis model was performed in independent cohorts from the ICGC database.Result: ANKZF1, ETS1, PLAUR, SERPINE1, FBP1 and PFKP were selected as hypoxia-related genetic signatures, and the resultant formula based on those genetic signatures and their respective coefficients helped generate RiskScore. The results of receiver operating characteristic (ROC) curve, risk plot, survival analysis and so on suggested that RiskScore based on hypoxia-related genetic signatures was an independent risk factor. A novel prognosis nomogram optimized via RiskScore showed its promising performance in both a TCGA-ccRCC cohort and an ICGC-ccRCC cohort.Conclusions: Our study reveals that the differential expressions of hypoxia-related genes are associated with the overall survival of patients with ccRCC. RiskScore based on hypoxia-related genetic signatures was an independent risk factor beyond TNM staging and grading. The novel nomogram optimized via RiskScore exhibited a promising prognostic ability. It may be able to serve as a prognostic tool for guiding clinical decisions and selecting effective individualized treatments.

scholarly journals LRRC19—A Bridge between Selenium Adjuvant Therapy and Renal Clear Cell Carcinoma: A Study Based on Datamining

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 440
Author(s):  
Yitong Zhang ◽  
Jiaxing Wang ◽  
Xiqing Liu
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Independent Risk Factor ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Cell Renal Cell Carcinoma ◽  
Low Expression

Kidney renal clear cell carcinoma (KIRC) is the most common and fatal subtype of renal cancer. Antagonistic associations between selenium and cancer have been reported in previous studies. Selenium compounds, as anti-cancer agents, have been reported and approved for clinical trials. The main active form of selenium in selenoproteins is selenocysteine (Sec). The process of Sec biosynthesis and incorporation into selenoproteins plays a significant role in biological processes, including anti-carcinogenesis. However, a comprehensive selenoprotein mRNA analysis in KIRC remains absent. In the present study, we examined all 25 selenoproteins and identified key selenoproteins, glutathione peroxidase 3 (GPX3) and type 1 iodothyronine deiodinase (DIO1), with the associated prognostic biomarker leucine-rich repeat containing 19 (LRRC19) in clear cell renal cell carcinoma cases from The Cancer Genome Atlas (TCGA) database. We performed validations for the key gene expression levels by two individual clear cell renal cell carcinoma cohorts, GSE781 and GSE6344, datasets from the Gene Expression Omnibus (GEO) database. Multivariate survival analysis demonstrated that low expression of LRRC19 was an independent risk factor for OS. Gene set enrichment analysis (GSEA) identified tyrosine metabolism, metabolic pathways, peroxisome, and fatty acid degradation as differentially enriched with the high LRRC19 expression in KIRC cases, which are involved in selenium therapy of clear cell renal cell carcinoma. In conclusion, low expression of LRRC19 was identified as an independent risk factor, which will advance our understanding concerning the selenium adjuvant therapy of clear cell renal cell carcinoma.

Proteomic stratification of clear cell renal cell carcinoma utilizing The Cancer Genome Atlas (TCGA) with external validation.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 406-406
Author(s):  
Samuel D. Kaffenberger ◽  
Giovanni Ciriello ◽  
Andrew G. Winer ◽  
Martin Henner Voss ◽  
Jodi Kathleen Maranchie ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
External Validation ◽  
Mtor Pathway ◽  
The Cancer Genome Atlas ◽  
Genomic Alterations ◽  
Cell Renal Cell Carcinoma ◽  
Cluster 2

406 Background: Proteomics represents the ultimate convergence of DNA and expression alterations. We therefore sought to leverage TCGA reverse phase protein array (RPPA) data with an independent proteomic platform to identify druggable targets and pathways associated with prognosis in clear cell renal cell carcinoma (ccRCC). Methods: Unsupervised hierarchical consensus clustering was performed and differentially expressed proteins were identified for pathway analysis. Associations with clinicogenomic factors were assessed and Cox proportional hazards models were performed for disease-specific survival (DSS). Results: RPPA clustering of 324 patients from the ccRCC TCGA revealed 5 robust clusters characterized by alterations in specific pathways and divergent prognoses. Cluster 1 was characterized by poor DSS, decreased expression of receptor tyrosine kinases (RTK) and upregulation of the mTOR pathway. It was also associated with mTOR pathway genomic alterations, sarcomatoid histology and the ccb prognostic mRNA signature (all p<0.001). Cluster 2 was characterized by increased expression of RTKs and interestingly, had upregulation of the mTOR pathway with excellent DSS. After accounting for stage and grade, cluster designation remained independently associated with DSS (HR 0.23 for cluster 2, 95% CI 0.08-0.68; p=0.008). External validation was performed on a separate cohort of 189 patients with a different quantitative proteomics platform. A panel of phosphoproteins (pHER1, pHER2, pHER3, pSHC, pMEK, pAKT), highly discriminant between the most divergent RPPA clusters (1 and 2) was evaluated. Those at the highest quartile of activation in > 3 proteins were associated with improved DSS (HR 0.19, 95% CI 0.05-0.082; p=0.03). Patients with mTOR pathway activation segregated to those with coincident RTK activation (n=83) and those without (n=13). Conclusions: We have identified and validated proteomic signatures which cluster ccRCC patients into 5 prognostic groups. Furthermore, two distinct mTOR-activated clusters—one with high RTK activity and one with increased mTOR pathway genomic alterations were revealed, which may have prognostic and therapeutic implications.

scholarly journals Association between visceral and subcutaneous adiposity and clinicopathological outcomes in non-metastatic clear cell renal cell carcinoma

2014 ◽  
Vol 8 (9-10) ◽  
pp. 675 ◽  
Author(s):  
Roy Mano ◽  
A Ari Hakimi ◽  
Emily C Zabor ◽  
Marta A Bury ◽  
Olivio F Donati ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Ct Scans ◽  
Study Cohort ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Pathologic Features ◽  
Subcutaneous Adiposity

Introduction: Visceral adiposity has been inconsistently associated with clinicopathologic features and outcomes of clear cell renal cell carcinoma (ccRCC); however, most studies were conducted in non-Western populations. We evaluated the associations between visceral and subcutaneous adiposity and clinicopathological characteristics of non-metastatic ccRCC patients in a Western population.Methods: The medical records of 220 surgically treated ccRCC patients with documented preoperative body mass index (BMI) and computed tomography (CT) scans were retrospectively reviewed. Nineteen patients with stage IV disease were excluded. Visceral (VFA) and subcutaneous fat area (SFA) were computed from preoperative CT scans. Correlations between obesity measures were assessed with Pearson correlation. Associations between obesity measures and pathologic features were evaluated using logistic regression models adjusted for sex. Overall survival (OS) probabilities were estimated using Cox regression analysis. The log-rank test was used for group comparisons.Results: The study cohort comprised 150 men and 51 women. Women had higher SFA (p = 0.01) but lower VFA (p < 0.001) than men. BMI was highly correlated with SFA (r = 0.804) and moderately correlated with VFA (r = 0.542). SFA and VFA were weakly correlated (r = 0.367). An increased BMI was associated with a better OS (p = 0.028). When adjusting for sex, neither SFA nor VFA was significantly associated with tumour grade, stage, or OS.Conclusions: Consistent with prior reports, our study suggests that increased BMI is associated with a better OS for patient with non-metastatic ccRCC. Despite the high correlation between SFA and BMI, neither SFA nor VFA were significantly associated with tumour stage, grade, or OS in the current study; however, further studies in larger cohorts are required to validate this finding. 

scholarly journals N6-Methyladenosine-Related Long Non-coding RNA Signature Associated With Prognosis and Immunotherapeutic Efficacy of Clear-Cell Renal Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Tianming Ma ◽  
Xiaonan Wang ◽  
Jiawen Wang ◽  
Xiaodong Liu ◽  
Shicong Lai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Differential Expression ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Signature ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

Increasing evidence suggests that N6-methyladenosine (m6A) and long non-coding RNAs (lncRNAs) play important roles in cancer progression and immunotherapeutic efficacy in clear-cell renal cell carcinoma (ccRCC). In this study, we conducted a comprehensive ccRCC RNA-seq analysis using The Cancer Genome Atlas data to establish an m6A-related lncRNA prognostic signature (m6A-RLPS) for ccRCC. Forty-four prognostic m6A-related lncRNAs (m6A-RLs) were screened using Pearson correlation analysis (|R| &gt; 0.7, p &lt; 0.001) and univariable Cox regression analysis (p &lt; 0.01). Using consensus clustering, the patients were divided into two clusters with different overall survival (OS) rates and immune status according to the differential expression of the lncRNAs. Gene set enrichment analysis corroborated that the clusters were enriched in immune-related activities. Twelve prognostic m6A-RLs were selected and used to construct the m6A-RLPS through least absolute shrinkage and selection operator Cox regression. We validated the differential expression of the 12 lncRNAs between tumor and non-cancerous samples, and the expression levels of four m6A-RLs were further validated using Gene Expression Omnibus data and Lnc2Cancer 3.0 database. The m6A-RLPS was verified to be an independent and robust predictor of ccRCC prognosis using univariable and multivariable Cox regression analyses. A nomogram based on age, tumor grade, clinical stage, and m6A-RLPS was generated and showed high accuracy and reliability at predicting the OS of patients with ccRCC. The prognostic signature was found to be strongly correlated to tumor-infiltrating immune cells and immune checkpoint expression. In conclusion, we established a novel m6A-RLPS with a favorable prognostic value for patients with ccRCC. The 12 m6A-RLs included in the signature may provide new insights into the tumorigenesis and allow the prediction of the treatment response of ccRCC.

scholarly journals Effect of Aberrant Long Noncoding RNA on the Prognosis of Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Han Wu ◽  
Haixiao Wu ◽  
Peng Sun ◽  
Desheng Zhu ◽  
Min Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Noncoding Rna ◽  
Risk Model ◽  
Clear Cell ◽  
Expression Profiles ◽  
Differential Expression Analysis ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

Clear cell renal cell carcinoma (ccRCC) is a kind of lethal cancer. Although there are mature treatment methods, there is still a lack of rigorous and scientific means for cancer diagnosis. Long noncoding RNAs (lncRNAs) are a kind of noncoding RNA (ncRNA). Recent studies find that alteration of lncRNA expression is related to the occurrence of many cancers. In order to find lncRNAs which can effectively predict the prognosis of ccRCC, RNA-seq count data and clinical information were downloaded from TCGA-KIRC, and gene expression profiles from 530 patients were included. Then, K -means was used for clustering, and the number of clusters was determined to be 5. The R-package “edgeR” was used to perform differential expression analysis. Subsequently, a risk model composed of 10 lncRNA biomarkers significantly related to prognosis was identified via Cox and LASSO regression analyses. Then, patients were divided into two groups according to the model-based risk score, and then, GSEA pathway enrichment was performed. The results showed that metabolism- and mTOR-related pathways were activated while immune-related pathways were inhibited in the high-risk patients. Combined with previous studies, it is believed that these 10 lncRNAs are potential targets for the treatment of ccRCC. In addition, Cox regression analysis was used to verify the independence of the risk model, and as results revealed, the risk model can be used to independently predict the prognosis of patients. In conclusion, our study found 10 lncRNAs related to the prognosis of ccRCC and provided new ideas for clinical diagnosis and drug development.

scholarly journals The ceRNA Network Has Potential Prognostic Value in Clear Cell Renal Cell Carcinoma: A Study Based on TCGA Database

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Haosheng Liu ◽  
Zhaowen Zhu ◽  
Jianxiong Fang ◽  
Tianqi Liu ◽  
Zhenhui Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Kidney Development ◽  
Cox Regression ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Cerna Network

Clear cell renal cell carcinoma (ccRCC) is a very common cancer in urology. Many evidences suggest that complex changed pathways take a nonnegligible part in the occurrence and development of ccRCC. Nevertheless, the underlying mechanism is not clear. In this study, the expression data between ccRCC and normal tissue samples in TCGA database were compared to distinguish differentially expressed genes (DEGs: mRNAs, miRNAs, and lncRNAs). Afterwards, we used GO enrichment and KEGG pathway enrichment analyses to explore the functions of these DEGs. We also found the correlation between three RNAs and created a competing endogenous RNA (ceRNA) network. Moreover, we used univariate Cox regression analysis to select DEGs that are connected with overall survival (OS) of ccRCC patients. We found 1652 mRNAs, 1534 lncRNAs, and 173 miRNAs that were distinguished in ccRCC compared with normal tissues. According to GO analysis, the maladjusted mRNAs are mainly concentrated in immune cell activation and kidney development, while according to KEGG, they are mainly concentrated in pathways related to cancer. A total of 5 mRNAs, 1 miRNA, and 4 lncRNAs were connected with patients’ OS. In this article, a network of lncRNA-miRNA-mRNA was established; it is expected to be able to indicate possible molecular mechanisms for initial of ccRCC and provide a new viewpoint for diagnosis of ccRCC.

scholarly journals Development and external validation of a pathological nodal staging score for patients with clear cell renal cell carcinoma

2018 ◽  
Vol 37 (8) ◽  
pp. 1631-1637
Author(s):  
Malte Rieken ◽  
Stephen A. Boorjian ◽  
Luis A. Kluth ◽  
Umberto Capitanio ◽  
Alberto Briganti ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
External Validation ◽  
Nodal Staging ◽  
Cell Renal Cell Carcinoma
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