Robustness of the 16-gene signature for prediction of recurrence-free interval in localized clear cell renal cell carcinoma.

455 Background: The Renal Cancer assay is a clinically validated RT-PCR assay developed to estimate the risk of recurrence in stage I-III clear cell renal cell carcinoma (ccRCC) patients (pts) treated with nephrectomy. The assay measures expression of 16 genes that are combined to calculate the Recurrence Score result (RS). The RS is associated with recurrence, renal cancer-specific survival and overall survival (all p<0.001) (Escudier, ASCO 2014). The performance of the RS in clinically relevant subgroups, compared to the Leibovich score, and its within-patient variability was examined. Methods: The algorithm, endpoints, methods, and analysis plan were pre-specified prior to merging clinical and molecular data. RT-PCR of RNA from fixed paraffin-embedded ccRCC tissue was performed without knowledge of clinical data. Recurrence-free internval (RFI) was analyzed using Cox regression stratified by stage with data censored at 5 years, and Kaplan-Meier methods. Multivariable models incorporating the Leibovich score were used to assess the additional contribution of the RS to prediction of recurrence. Within- and between-tumor block reproducibility was assessed in an independent study using two separate tumor blocks from 8 pts, where each block was analyzed at 3 depths. Results: RS was generated in 626/645 pts (97%): 398 stage I, 54 stage II, 174 stage III. Median follow up was 5.5 yrs. The RS was significantly associated with risk of recurrence after adjustment for the Leibovich score (HR=4.20, p<0.001). Additionally, the performance of RS was similar across age groups (<60, 60-70 or ≥70), gender, nephrectomy type, tumor size (≤4, 4-7 or >7cm), grade, and presence/absence of invasion (all interaction p>0.29). Within-patient variability in the score (std. dev. of 1.73 and 4.74 RS units for within- and between-tumor block, respectively) was lower than patient-to-patient variability (std. dev. of 15.6 in validation study). Conclusions: The 16-gene signature remains strongly associated with risk of recurrence after adjustment for the Leibovich score and performs consistently across clinically relevant subgroups. Examination of within-patient and between-patient variability indicates that the score is robust to tumor heterogeneity.

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Validation of a 16-gene signature for prediction of recurrence after nephrectomy in stage I-III clear cell renal cell carcinoma (ccRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.15_suppl.4502 ◽

2014 ◽

Vol 32 (15_suppl) ◽

pp. 4502-4502 ◽

Cited By ~ 2

Author(s):

Bernard J. Escudier ◽

Serge Koscielny ◽

Margarita Lopatin ◽

Christer Svedman ◽

Virginie Verkarre ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Gene Signature ◽

Stage I ◽

Cell Renal Cell Carcinoma

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Development of a novel gene signature to predict prognosis and response to PD-1 blockade in clear cell renal cell carcinoma

OncoImmunology ◽

10.1080/2162402x.2021.1933332 ◽

2021 ◽

Vol 10 (1) ◽

pp. 1933332

Author(s):

Xiaomao Yin ◽

Zaoyu Wang ◽

Jianfeng Wang ◽

Yunze Xu ◽

Wen Kong ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Gene Signature ◽

Cell Renal Cell Carcinoma ◽

Novel Gene

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Bioinformatic analysis identifies potentially key differentially expressed genes in oncogenesis and progression of clear cell renal cell carcinoma

PeerJ ◽

10.7717/peerj.8096 ◽

2019 ◽

Vol 7 ◽

pp. e8096 ◽

Cited By ~ 2

Author(s):

Haiping Zhang ◽

Jian Zou ◽

Ying Yin ◽

Bo Zhang ◽

Yaling Hu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Differentially Expressed Genes ◽

Renal Cell ◽

Molecular Mechanisms ◽

Clear Cell ◽

Clinical Stage ◽

Stage I ◽

Differentially Expressed ◽

Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) is one of the most common and lethal types of cancer within the urinary system. Great efforts have been made to elucidate the pathogeny. However, the molecular mechanism of ccRCC is still not well understood. The aim of this study is to identify key genes in the carcinogenesis and progression of ccRCC. The mRNA microarray dataset GSE53757 was downloaded from the Gene Expression Omnibus database. The GSE53757 dataset contains tumor and matched paracancerous specimens from 72 ccRCC patients with clinical stage I to IV. The linear model of microarray data (limma) package in R language was used to identify differentially expressed genes (DEGs). The protein–protein interaction (PPI) network of the DEGs was constructed using the search tool for the retrieval of interacting genes (STRING). Subsequently, we visualized molecular interaction networks by Cytoscape software and analyzed modules with MCODE. A total of 1,284, 1,416, 1,610 and 1,185 up-regulated genes, and 932, 1,236, 1,006 and 929 down-regulated genes were identified from clinical stage I to IV ccRCC patients, respectively. The overlapping DEGs among the four clinical stages contain 870 up-regulated and 645 down-regulated genes. The enrichment analysis of DEGs in the top module was carried out with DAVID. The results showed the DEGs of the top module were mainly enriched in microtubule-based movement, mitotic cytokinesis and mitotic chromosome condensation. Eleven up-regulated genes and one down-regulated gene were identified as hub genes. Survival analysis showed the high expression of CENPE, KIF20A, KIF4A, MELK, NCAPG, NDC80, NUF2, TOP2A, TPX2 and UBE2C, and low expression of ACADM gene could be involved in the carcinogenesis, invasion or recurrence of ccRCC. Literature retrieval results showed the hub gene NDC80, CENPE and ACADM might be novel targets for the diagnosis, clinical treatment and prognosis of ccRCC. In conclusion, the findings of present study may help us understand the molecular mechanisms underlying the carcinogenesis and progression of ccRCC, and provide potential diagnostic, therapeutic and prognostic biomarkers.

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A prognostic nomogram based on competing endogenous RNA network for clear-cell renal cell carcinoma

10.21203/rs.3.rs-19720/v1 ◽

2020 ◽

Author(s):

Yun Peng ◽

Shangrong Wu ◽

Zihan Xu ◽

Dingkun Hou ◽

Nan Li ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Rna Sequencing ◽

Renal Cell ◽

Cox Regression ◽

Clear Cell ◽

Gene Signature ◽

Expression Data ◽

Competing Endogenous Rna ◽

Cell Renal Cell Carcinoma

Abstract Backgroud Clear-cell renal cell carcinoma (ccRCC) is stubborn to traditional chemotherapy and radiation treatment, which makes its clinical management a major challenge. Recently, we have made efforts to understand the etiology of ccRCC. Increasing evidence revealed that the competing endogenous RNA (ceRNA) were involved in the development of various tumor. However, it’s scant for studying on ccRCC, and a comprehensive analysis of prognostic model based on lncRNA-miRNA-mRNA ceRNA regulatory network of ccRCC with large-scale sample size and RNA‐sequencing expression data is still limited. Methods RNA‐sequencing expression data were taken out from GTEx database and TCGA database, A total of 354 samples with ccRCC and 157 normal controlled samples were included in our study. The ccRCC-specific genes were obtained from WGCNA and differential expression analysis. Following, the communication between mRNAs and lncRNAs and target miRNAs were predicted by MiRcode, starBase, miRTarBase, and TargetScan. A gene signature of eight genes was constructed by univariate Cox regression, lasso methods and multivariate Cox regression analysis. Results A total of 2191 mRNAs and 1377 lncRNAs was identified, and a dys-regulated ceRNA network for ccRCC was established using 7 mRNAs, 363 lncRNAs, and 3 miRNAs. Further, a gene signature in cluding 8 genes based on this ceRNA was constructed, meanwhile, a nomogram predicting 1-, 3-, 5-year survival probability containing both clinical characteristics and ccRCC-specific gene signatures was developed. Conclusion It could contribute to a better understanding of ccRCC tumorigenesis mechanism and guide clinicians to make a more accurate treatment decision.

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Individualized immune-related gene signature predicts immune status and oncologic outcomes in clear cell renal cell carcinoma patients

Urologic Oncology Seminars and Original Investigations ◽

10.1016/j.urolonc.2019.09.014 ◽

2020 ◽

Vol 38 (1) ◽

pp. 7.e1-7.e8 ◽

Cited By ~ 3

Author(s):

Ying Xiong ◽

Li Liu ◽

Qi Bai ◽

Yu Xia ◽

Yang Qu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Immune Status ◽

Clear Cell ◽

Gene Signature ◽

Oncologic Outcomes ◽

Related Gene ◽

Cell Renal Cell Carcinoma ◽

Immune Related Gene

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A four-gene signature predicts survival in clear-cell renal-cell carcinoma

Oncotarget ◽

10.18632/oncotarget.12631 ◽

2016 ◽

Vol 7 (50) ◽

pp. 82712-82726 ◽

Cited By ~ 17

Author(s):

Jun Dai ◽

Yuchao Lu ◽

Jinyu Wang ◽

Lili Yang ◽

Yingyan Han ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Clear Cell ◽

Gene Signature ◽

Cell Renal Cell Carcinoma

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Survival outcomes and patterns of utilization of cytoreductive nephrectomy in the tyrosine kinase inhibitors (TKI)-era in metastatic clear cell renal cell carcinoma (ccRCC) and non-clear cell renal cell carcinoma (nccRCC): Analyses from the National Cancer Database (NCDB).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e16068 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e16068-e16068

Author(s):

Jeanny B. Aragon-Ching ◽

Hongkun Wang ◽

Donald L. Trump

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Median Survival ◽

Renal Cell ◽

Clear Cell ◽

Stage Iv ◽

Stage I ◽

Survival Outcomes ◽

Cytoreductive Nephrectomy ◽

Cell Renal Cell Carcinoma

e16068 Background: Use of TKIs is standard of care for metastatic ccRCC and cytoreductive nephrectomy has improved survival even in metastatic ccRCC. The use of cytoreductive nephrectomy in the TKI era post-2005 for nccRCC histologies is unknown. We sought to determine trends and explore differences in characteristics of ccRCC and nccRCC, use of cytoreductive nephrectomy and survival outcomes for varying stages. Methods: Using a de-identified dataset acquired from the NCDB from 2004 to 2014, extraction of demographic information on patients divided into ccRCC versus nccRCC. Descriptive statistics was used for summarizing patients’ characteristics. Chi-Square test was used for comparing categorical variables. Two-sample t-test was used for comparing continuous variables. Kaplan-Meier method was used to analyze patients’ survival data. Results: 302,339 (82%) ccRCC and 66,530 (18%) nccRCC patients were identified. nccRCC included papillary (n = 42,251), sarcomatoid (n = 5769), chromophobe (n = 17,671) and collecting duct (n = 839). The median age for both groups was 63 years, more common in males (ccRCC = 61%; nccRCC = 69%), and mostly Caucasians (ccRCC = 86%; nccRCC = 75%). Most patients were treated in comprehensive community and academic research programs (ccRCC = 81%; nccRCC = 83%). Majority of patients were diagnosed with AJCC Stage I (ccRCC = 57%, nccRCC = 62%). Stage IV was diagnosed in 14% of ccRCC and 9% of nccRCC. The utilization of nephrectomy declined for ccRCC at 36% in the year 2014 compared to 44% in 2005, whereas it declined more for nccRCC with 47% in 2014 compared to 70% in 2005. The median survival time for Stage I was comparable in both groups (ccRCC = 140 mos, 95% CI 138.8 – 142.16; nccRCC = 140 mos, 95% CI 138 – unestimable). However, median survival was worse for stage IV in nccRCC (ccRCC = 9 mos; 95% CI 8.8 – 9.17; nccRCC = 7.43 mos; 95% CI 7.16 – 7.79). Conclusions: In stage IV patients with nccRCC, cytoreductive nephrectomy is used less often and overall survival appears inferior compared to ccRCC.

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