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. 

Loss of BAP1 and PBRM1 protein expression and its association with clear cell renal cell carcinoma-specific survival.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 414-414 ◽  
Author(s):  
Richard Wayne Joseph ◽  
Payal Kapur ◽  
Daniel Serie ◽  
Jeanette Eckel-Passow ◽  
Thai Huu Ho ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Clinical Outcomes ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Pathologic Features ◽  
The Impact

414 Background: While mutations in PBRM1 (~40%) and BAP1(~10%) are associated with clinical outcomes and pathologic features in clear cell renal cell carcinoma (ccRCC), the impact of protein expression of these genes remains unknown. Herein, we quantify PBRM1/BAP1 protein expression in a large cohort of patients with localized ccRCC and associate expression with cancer-specific survival (CSS) and pathologic features. Methods: We utilized the Mayo Clinic Renal Registry and identified 1,416 patients who underwent nephrectomy to treat clinically localized ccRCC between 1/3/1990 and 4/14/2009. We used immunohistochemistry (IHC) to detect PBRM1/BAP1 expression, and a central pathologist blinded to the outcomes scored tumors as either positive or negative. Tumors with heterogeneous or equivocal staining were excluded from this analysis. We generated Cox proportional hazard regression models for associations with ccRCC-SS, and we employed Mann-Whitney U tests for associations with pathologic features. Results: Of the 1,416 samples, 1,232 (87%) were PBRM1/BAP1 positive or negative, 163 (11%) had heterogeneous staining, and 21 (1%) could not be assessed. The distribution and association of PBRM1/BAP1 phenotypes with clinical outcomes are listed in the table below. PBRM1+/BAP1+ tumors have the best CSS, and PBRM1-/BAP1- have the worst. In addition, PBRM1/BAP1 expression strongly associated with the tumor size, stage, grade, and tumor necrosis (p<0.0001). Conclusions: This study is the first and largest to quantify PRBM1/BAP1 protein expression in ccRCC tumors. We were able to quantify PBRM1/BAP1 through IHC in the vast majority of tumors (87%), and PRBM1/BAP1 expression strongly associates with both CSS and pathologic tumor characteristics. Our data confirms our previous findings of the importance of PRBM1/BAP1 in the molecular pathogenesis of ccRCC. [Table: see text]

Greater body mass index is associated with better pathologic features and improved outcome among patients treated surgically for clear cell renal cell carcinoma

Urology ◽  
2006 ◽  
Vol 68 (4) ◽  
pp. 741-746 ◽  
Author(s):  
Alexander S. Parker ◽  
Christine M. Lohse ◽  
John C. Cheville ◽  
David D. Thiel ◽  
Bradley C. Leibovich ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Body Mass ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Pathologic Features ◽  
Improved Outcome

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.

Association of topoisomerase II expression and cancer-specific death in patients with surgically resected clear cell renal cell carcinoma.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
Faithlore Patrice Gardner ◽  
Richard Wayne Joseph ◽  
Daniel Serie ◽  
Tracy W. Hilton ◽  
Mansi Parasramka ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Risk Of Death ◽  
Pathologic Features ◽  
Increased Risk ◽  
Risk Of Cancer

446 Background: Despite the development of prognostic algorithms based on clinico-pathologic features, the ability to identify aggressive forms of clear cell renal cell carcinoma (ccRCC) remains suboptimal. Topoisomerase IIA (TOP2a) is a biomarker of DNA replication and a target for antineoplastic agents. Herein, we evaluate the association of TOP2a expression in ccRCC tumors with pathologic features of aggressiveness and risk of cancer-specific death. Methods: We identified 947 patients who underwent nephrectomy to treat clinically localized ccRCC between January 16, 1990, and September 27, 2006. TOP2a expression was assessed using IHC and scored as number of positive cells per mm2. We evaluated TOP2a expression using a continuous variable and tertile categories. For associations with pathologic features, we employed Kruskal-Wallis tests and for associations with cancer-specific survival, we generated Cox proportional hazard regression models. Results: HigherTOP2a expression is associated with later stage, higher grade and higher Mayo SSIGN score (all p < 0.001). The risk of death from RCC increases with increasing TOP2a expression (p trend < 0.0001). Compared to patients in the lowest tertile, those patients with tumors in the highest tertile of TOP2a expression were at increased risk of RCC death (HR=2.31 95% CI 1.64-3.25; p < 0.0001). Interestingly, among those patients with low risk disease (SSIGN score 0-3; ~95% 10 year survival), those with high TOP2a were at increased risk of RCC death (HR=3.09 95% CI 1.29-7.40; p = 0.01). Conclusions: Higher TOP2a expression is associated with more aggressive pathologic features and increased risk of cancer-specific death among patients undergoing surgery for localized ccRCC. If confirmed, these data support further inquiry for TOP2a as a prognostic and predictive biomarker for ccRCC patients.

scholarly journals Identification of a Six-Gene Prognostic Signature Characterized by Tumor Microenvironment Immune Profiles in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Lu Zhang ◽  
Jianlong Li ◽  
Mengzhao Zhang ◽  
Lu Wang ◽  
Tao Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Microenvironment ◽  
Risk Stratification ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Prognostic Signature ◽  
Characteristic Analysis ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

Clear cell renal cell carcinoma (ccRCC) is widely acknowledged to be extremely sensitive to immunotherapy, emphasizing the tremendous impacts on which the tumor microenvironment (TME) has shown. However, the molecular subgroups characterized by the TME features scarcely serve as the risk stratification guides in clinical practice for survival outcomes and immunotherapy response prediction. This study generated fresh insights into a novel TME-related prognostic signature derived from The Cancer Genome Atlas database using integrated bioinformatics analyses. Subsequently, Kaplan–Meier survival analysis, receiver operating characteristic analysis, and univariate and multivariate Cox regression analysis were performed to evaluate and validate the efficacy and the accuracy of the signature in ccRCC prognosis. Furthermore, we discovered that the risk score presented an increased likelihood of correlation with miscellaneous clinicopathological characteristics, natural killer cell-mediated cytotoxicity, immune cell infiltration levels, and immune checkpoint expression. These findings highlighted the notion that the six-gene signature characterized by the TME features may have implications on the risk stratification for personalized and precise immunotherapeutic management.

scholarly journals Characterization of Hypoxia-Related Molecular Subtypes in Clear Cell Renal Cell Carcinoma to Aid Immunotherapy and Targeted Therapy via Multi-Omics Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Weimin Zhong ◽  
Hongbin Zhong ◽  
Fengling Zhang ◽  
Chaoqun Huang ◽  
Yao Lin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Somatic Mutations ◽  
Clear Cell ◽  
Molecular Subtypes ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Tumor Purity

Objective: Tumor hypoxia is a key factor in resistance to anti-cancer treatment. Herein, this study aimed to characterize hypoxia-related molecular subtypes and assess their correlations with immunotherapy and targeted therapy in clear cell renal cell carcinoma (ccRCC).Materials: We comprehensively analyzed copy number variation (CNV), somatic mutation, transcriptome expression profile and clinical information for ccRCC from TCGA and ICGC databases. Based on 98 prognosis-related hypoxia genes, samples were clustered using unsupervized non-negative matrix factorization (NMF) analysis. We characterized the differences between subtypes concerning prognosis, CNV, somatic mutations, pathways, immune cell infiltrations, stromal/immune scores, tumor purity, immune checkpoint inhibitors (ICI), response to immunotherapy and targeted therapy and CXC chemokines. Based on differentially expressed genes (DEGs) between subtypes, a prognostic signature was built by LASSO Cox regression analysis, followed by construction of a nomogram incorporating the signature and clinical features.Results: Two hypoxia-related molecular subtypes (C1 and C2) were constructed for ccRCC. Differential CNV, somatic mutations and pathways were found between subtypes. C2 exhibited poorer prognosis, higher immune/stromal scores, and lower tumor purity than C1. Furthermore, C2 had more sensitivity to immunotherapy and targeted therapy than C1. The levels of CXCL1/2/3/5/6/8 chemokines in C2 were distinctly higher than in C1. Consistently, DEGs between subtypes were significantly enriched in cytokine-cytokine receptor interaction and immune responses. This subtype-specific signature can independently predict patients’ prognosis. Following verification, the nomogram could be utilized for personalized prediction of the survival probability.Conclusion: Our findings characterized two hypoxia-related molecular subtypes for ccRCC, which can assist in identifying high-risk patients with poor clinical outcomes and patients who can benefit from immunotherapy or targeted therapy.

scholarly journals A New Prognostic Risk Signature of Eight Ferroptosis-Related Genes in the Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji Chen ◽  
Yating Zhan ◽  
Rongrong Zhang ◽  
Bo Chen ◽  
Junting Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Locally Advanced ◽  
Lasso Regression ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

Clear cell renal cell carcinoma (ccRCC) is the most common renal cell carcinoma and has poor prognosis in the locally advanced stage. Ferroptosis, a relatively new type of cell death, has gained significant attention in recent years. This study aimed to explore the prognostic value of ferroptosis-related genes (FRGs) in ccRCC. In this study, 50 differentially expressed FRGs between ccRCC and adjacent normal kidney tissues were identified, 26 of them correlated with overall survival (OS) (P &lt;0.05). Eight optimal FRGs were selected by Lasso regression and multivariate Cox regression analysis, and used to construct a new prognostic risk signature to predict the prognosis of ccRCC patients. In addition, the signature passed the validation of prognostic survival analyses by a significant margin, and the risk score was identified as an independent prognostic marker via Cox regression analyses. Further studies indicated that the signature was significantly correlated with immune cell infiltration. Moreover, the levels of eight FRGs were examined in ccRCC. Collectively, the 8-FRG prognostic risk signature helps the clinicians predict the prognosis and OS of the patients, and standardize prognostic assessments.

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.

Sign in / Sign up

Export Citation Format

Share Document