scholarly journals Clinicopathological and Molecular Prognostic Classifier for Intermediate/High-Risk Clear Cell Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6338
Author(s):  
Fiorella L. Roldán ◽  
Juan J. Lozano ◽  
Mercedes Ingelmo-Torres ◽  
Raquel Carrasco ◽  
Esther Díaz ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Accuracy ◽  
Molecular Model ◽  
Expression Patterns ◽  
Cell Renal Cell Carcinoma

The probability of tumor progression in intermediate/high-risk clear cell renal cell carcinoma (ccRCC) is highly variable, underlining the lack of predictive accuracy of the current clinicopathological factors. To develop an accurate prognostic classifier for these patients, we analyzed global gene expression patterns in 13 tissue samples from progressive and non-progressive ccRCC using Illumina Hi-seq 4000. Expression levels of 22 selected differentially expressed genes (DEG) were assessed by nCounter analysis in an independent series of 71 ccRCCs. A clinicopathological-molecular model for predicting tumor progression was developed and in silico validated in a total of 202 ccRCC patients using the TCGA cohort. A total of 1202 DEGs were found between progressive and non-progressive intermediate/high-risk ccRCC in RNAseq analysis, and seven of the 22 DEGs selected were validated by nCounter. Expression of HS6ST2, pT stage, tumor size, and ISUP grade were found to be independent prognostic factors for tumor progression. A risk score generated using these variables was able to distinguish patients at higher risk of tumor progression (HR 7.27; p < 0.001), consistent with the results obtained from the TCGA cohort (HR 2.74; p < 0.002). In summary, a combined prognostic algorithm was successfully developed and validated. This model may aid physicians to select high-risk patients for adjuvant therapy.

scholarly journals A Mitochondrial Dysfunction and Oxidative Stress Pathway-Based Prognostic Signature for Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-32
Author(s):  
Yue Wu ◽  
Xi Zhang ◽  
Xian Wei ◽  
Huan Feng ◽  
Bintao Hu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Risk Group ◽  
Prognostic Significance ◽  
Individual Risk ◽  
Cell Renal Cell Carcinoma

Mitochondria not only are the main source of ATP synthesis but also regulate cellular redox balance and calcium homeostasis. Its dysfunction can lead to a variety of diseases and promote cancer and metastasis. In this study, we aimed to explore the molecular characteristics and prognostic significance of mitochondrial genes (MTGs) related to oxidative stress in clear cell renal cell carcinoma (ccRCC). A total of 75 differentially expressed MTGs were analyzed from The Cancer Genome Atlas (TCGA) database, including 46 upregulated and 29 downregulated MTGs. Further analysis screened 6 prognostic-related MTGs (ACAD11, ACADSB, BID, PYCR1, SLC25A27, and STAR) and was used to develop a signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses showed that the signature could accurately distinguish patients with poor prognosis and had good individual risk stratification and prognostic potential. Stratified analysis based on different clinical variables indicated that the signature could be used to evaluate tumor progression in ccRCC. Moreover, we found that there were significant differences in immune cell infiltration between the low- and high-risk groups based on the signature and that ccRCC patients in the low-risk group responded better to immunotherapy than those in the high-risk group (46.59% vs 35.34%, P = 0.008 ). We also found that the expression levels of these prognostic MTGs were significantly associated with drug sensitivity in multiple ccRCC cell lines. Our study for the first time elucidates the biological function and prognostic significance of mitochondrial molecules associated with oxidative stress and provides a new protocol for evaluating treatment strategies targeting mitochondria in ccRCC patients.

scholarly journals Development and Interpretation of a Genomic Instability Derived lncRNAs Based Risk Signature as a Predictor of Prognosis for Clear Cell Renal Cell Carcinoma Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Huiying Yang ◽  
Xiaoling Xiong ◽  
Hua Li
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Genomic Instability ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Cell Renal Cell Carcinoma ◽  
Prognosis Prediction

BackgroundClear cell renal cell carcinoma (ccRCC) is a kind of frequently diagnosed cancer, leading to high death rate in patients. Genomic instability (GI) is regarded as playing indispensable roles in tumorigenesis and impacting the prognosis of patients. The aberrant regulation of long non-coding RNAs (lncRNAs) is a main cause of GI. We combined the somatic mutation profiles and expression profiles to identify GI derived lncRNAs (GID-lncRNAs) in ccRCC and developed a GID-lncRNAs based risk signature for prognosis prediction and medication guidance.MethodsWe decided cases with top 25% cumulative number of somatic mutations as genomically unstable (GU) group and last 25% as genomically stable (GS) group, and identified differentially expressed lncRNAs (GID-lncRNAs) between two groups. Then we developed the risk signature with all overall survival related GID-lncRNAs with least absolute shrinkage and selection operator (LASSO) Cox regression. The functions of the GID-lncRNAs were partly interpreted by enrichment analysis. We finally validated the effectiveness of the risk signature in prognosis prediction and medication guidance.ResultsWe developed a seven-lncRNAs (LINC00460, AL139351.1, AC156455.1, AL035446.1, LINC02471, AC022509.2, and LINC01606) risk signature and divided all samples into high-risk and low-risk groups. Patients in high-risk group were in more severe clinicopathologic status (higher tumor grade, pathological stage, T stage, and more metastasis) and were deemed to have less survival time and lower survival rate. The efficacy of prognosis prediction was validated by receiver operating characteristic analysis. Enrichment analysis revealed that the lncRNAs in the risk signature mainly participate in regulation of cell cycle, DNA replication, material metabolism, and other vital biological processes in the tumorigenesis of ccRCC. Moreover, the risk signature could help assess the possibility of response to precise treatments.ConclusionOur study combined the somatic mutation profiles and the expression profiles of ccRCC for the first time and developed a GID-lncRNAs based risk signature for prognosis predicting and therapeutic scheme deciding. We validated the efficacy of the risk signature and partly interpreted the roles of the seven lncRNAs composing the risk signature in ccRCC. Our study provides novel insights into the roles of genomic instability derived lncRNAs in ccRCC.

scholarly journals MMP9 and IGFBP1 Regulate Tumor Immune and Drive Tumor Progression in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 12 (8) ◽  
pp. 2243-2257
Author(s):  
Tianbo Xu ◽  
Su Gao ◽  
Jingchong Liu ◽  
Yu Huang ◽  
Ke Chen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

αB-Crystallin in clear cell renal cell carcinoma: Tumor progression and prognostic significance

2013 ◽  
Vol 31 (7) ◽  
pp. 1367-1377 ◽  
Author(s):  
Pei-Yin Ho ◽  
Shih-Chieh Chueh ◽  
Shyh-Horng Chiou ◽  
Shuo-Meng Wang ◽  
Wei-Chou Lin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Progression ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Prognostic Significance ◽  
Cell Renal Cell Carcinoma ◽  
Αb Crystallin ◽  
Carcinoma Tumor

scholarly journals Identification of high-risk patients with clear cell renal cell carcinoma based on interphase-FISH

2014 ◽  
Vol 110 (10) ◽  
pp. 2537-2543 ◽  
Author(s):  
J Sanjmyatav ◽  
S Matthes ◽  
M Muehr ◽  
D Sava ◽  
M Sternal ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Interphase Fish ◽  
High Risk Patients ◽  
Risk Patients

Use of preoperative C-reactive protein to improve predictive accuracy in clear cell renal cell carcinoma.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 474-474
Author(s):  
Stephan Kruck ◽  
Felix K. Chun ◽  
Axel S. Merseburger ◽  
Hossein Tezval ◽  
Marcus Scharpf ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Accuracy ◽  
Tnm Stage ◽  
C Reactive Protein ◽  
Cell Renal Cell Carcinoma ◽  
Reactive Protein ◽  
Karnofsky Index

474 Background: White blood cell count (WBC) and C-reactive protein (CRP) are reliable biomarkers in clear cell renal cell carcinoma (ccRCC). Nevertheless, accepted cut-offs values for risk stratifications are missing. This study re-evaluated the prognostic and predictive significance of preoperatively WBC and CRP that independently predicts patient prognosis and to determine optimal cut-off values for CRP. Methods: 327 patients with surgery for ccRCC were retrospectively evaluated from 1996 to 2005. Cox-proportional hazard models were used, adjusted for the effects of tumor stage, tumor size, Fuhrman grade, and Karnofsky-Index; and to evaluate the prognostic significance of WBC and CRP; and to identify cut-off values. Identified cut-offs were correlated with clinico-pathological parameters and used to estimate cancer-specific survival (CSS). To prove any additional predictive accuracy of the identified cut-off it was compared to a clinico-pathological base model using Harrell c-index. Results: In univariable analyses WBC was a significant prognostic marker at a concentration of 9.5/µl (HR: 1.83) and 11.0/µl (HR: 2.09) and supported a CRP value of 0.25 mg/dL (HR: 6.47, p < 0.001) and 0.5mg/dL (HR: 7.15, p < 0.001) as potential cut-off values. If adjusted by the multivariable models WBC showed no clear breakpoint, but a CRP-value of 0.25mg/dL (HR: 2.80, p = 0.027) proved to be optimal. Reduced CSS was proven for CRP 0.25 mg/dL (median: 69.9 vs. 92.3 months). Median follow-up was 57.5 months with 72 (22%) tumor related deaths. The final model built by the addition of CRP 0.25mg/dL did not improve predictive accuracy (c-index = 0.877) than compared to the clinico-pathological base model (c-index =0.881) which included TNM-stage, grading and Karnofsky-Index. Conclusions: Multivariable analyses revealed an optimal breakpoint of CRP at a value of 0.25mg/dL best to stratify patients at risk of cancer-specific mortality, but CRP 0.25mg/dL added no additional information in the prediction model. Therefore we cannot recommend to measure CRP as the traditional parameters of TNM-stage, grading and Karnofsky-Index were already of high predictive accuracy.

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