scholarly journals Development of an Individualized Ubiquitin Prognostic Signature for Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Yue Wu ◽  
Xi Zhang ◽  
Xian Wei ◽  
Huan Feng ◽  
Bintao Hu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Good Prediction ◽  
Tumor Type ◽  
Prognostic Signature ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis ◽  
Good Prediction Accuracy

Clear cell renal cell carcinoma (ccRCC) is a common tumor type in genitourinary system and has a poor prognosis. Ubiquitin dependent modification systems have been reported in a variety of malignancies and have influenced tumor genesis and progression. However, the molecular characteristics and prognostic value of ubiquitin in ccRCC have not been systematically reported. In our study, 204 differentially expressed ubiquitin related genes (URGs) were identified from The Cancer Genome Atlas (TCGA) cohort, including 141 up-regulated and 63 down-regulated URGs. A total of seven prognostic related URGs (CDCA3, CHFR, CORO6, RNF175, TRIM72, VAV3, and WDR72) were identified by Cox regression analysis of differential URGs and used to construct a prognostic signature. Kaplan-Meier analysis confirmed that high-risk patients had a worse prognosis (P = 1.11e-16), and the predicted area under the receiver operating characteristic (ROC) curves were 0.735 at 1 year, 0.702 at 3 years, and 0.744 at 5 years, showing good prediction accuracy. Stratified analysis showed that the URGs-based prognostic signature could be used to evaluate tumor progression in ccRCC. Further analysis confirmed that the signature is an independent prognostic factor related to the prognosis of ccRCC patients, which may help to reveal the molecular mechanism of ccRCC and provide potential diagnostic and prognostic markers for ccRCC.

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| > 0.7, p < 0.001) and univariable Cox regression analysis (p < 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 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 Ferroptosis-Related Gene Signature Accurately Predicts Survival Outcomes in Patients With Clear-Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Kaili Chang ◽  
Chong Yuan ◽  
Xueguang Liu
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Signature ◽  
Receptor Interaction ◽  
Related Gene ◽  
Prognostic Signature ◽  
Cell Renal Cell Carcinoma ◽  
Cox Regression Analysis

As a type of regulated cell death induced by Ras selective lethal (RSL) compounds such as erasti, ferroptosis is characterized by iron-dependent lipid peroxide accumulation to lethal levels. At present, little is known about the role of ferroptosis-related genes in clear-cell renal cell carcinoma (ccRCC). In the present study, the expression data of ferroptosis-related genes in ccRCC were obtained from the Cancer Genome Atlas (TCGA), and COX regression analysis was performed to construct a risk model of ferroptosis prognostic signature. The GEO database was used to verify the accuracy of the model. The following findings were made: the results reveal that the prognostic signature constructed by 11 ferroptosis genes (CARS, CD44, DPP4, GCLC, HMGCR, HSPB1, NCOA4, SAT1, PHKG2, GOT1, HMOX1) was significantly related to the overall survival (OS) of ccRCC patients based on the lowest Akaike information criterion (AIC); multivariate analysis indicates that ferroptosis-related gene prognostic signature was an independent prognostic factor in ccRCC patients; the calibration curve and c-index value (0.77) demonstrate that the nomogram with the signature could predict the survival of ccRCC patients; and enrichment analysis shows that the high-risk group were enriched in humoral immunity and receptor interaction pathways. The aforementioned findings indicate that the ferroptosis-related gene signature can accurately predict the prognosis of ccRCC patients and provide valuable insights for individualized treatment.

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 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 Similarities and Differences between Clear Cell Tubulo-Papillary and Conventional Clear Cell Renal Cell Carcinoma: A Comparative Phenotypical and Mutational Analysis

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 123
Author(s):  
Francesca Giunchi ◽  
Tania Franceschini ◽  
Elisa Gruppioni ◽  
Annalisa Altimari ◽  
Elisa Capizzi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Mutational Analysis ◽  
Papillary Renal Cell Carcinoma ◽  
Tumor Type ◽  
Wild Type ◽  
Cell Renal Cell Carcinoma

Background: Clear cell tubulo-papillary renal cell carcinoma (cctpRCC) is characterized by clear cell morphology, but differs from conventional clear cell carcinoma (ccRCC) for its indolent clinical behavior and genetic background. The differential diagnosis between the two is based on histology and immunohistochemistry (IHC). Methods: We performed a comparative case-control histological, IHC, and genetic analysis by next generation sequencing (NGS), to point out the differences in 10 cases of cctpRCC, and six controls of ccRCC with low stage and grade. Results: All 16 cases showed the IHC profile with cytokeratin 7, racemase, and carbonic anhydrase IX expected for the histological features of each tumor type. By contrast, the NGS mutation analysis that covered 207 amplicons of 50 oncogenes or tumor suppressor genes provided conflicting results. Among the 10 cctpRCC cases, eight (80%) were wild type for all of the genes in the panel, while two (20%) harbored VHL mutations typical of ccRCC. Three of the six (50%) ccRCC control cases showed expected VHL mutations; two (33%) harbored pathogenic mutations in the p53 or the CKIT genes; and one (16%) was wild type. Conclusion: We can assume that histology and ICH are not sufficient for a definitive diagnosis of cctpRCC or ccRCC. Although with a panel covering 50 genes, we found that 80% of cctpRCC were genetically silent; thus, suggesting an indolent biology of these tumors. The differential diagnosis between ccptRCC and ccRCC for the choice of the best therapeutic strategy likely requires the comprehensive evaluation of histology, IHC, and at least VHL mutations.

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