scholarly journals A 17-Gene Signature Predicted Prognosis in Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Fan Li ◽  
Weifeng Hu ◽  
Wei Zhang ◽  
Guohao Li ◽  
Yonglian Guo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Prognostic Indicators ◽  
Incidence And Mortality ◽  
Tcga Dataset

Renal cell carcinoma (RCC), which was one of the most common malignant tumors in urinary system, had gradually increased incidence and mortality in recent years. Although significant advances had been made in molecular and biology research on the pathogenesis of RCC, effective treatments and prognostic indicators were still lacking. In order to predict the prognosis of RCC better, we identified 17 genes that were associated with the overall survival (OS) of RCC patients from The Cancer Genome Atlas (TCGA) dataset and a 17-gene signature was developed. Through SurvExpress, we analyzed the expression differences of the 17 genes and their correlation with the survival of RCC patients in five datasets (ZHAO, TCGA, KIPAN, KIRC, and KIRP), and then evaluated the survival prognostic significance of the 17-gene signature for RCC. Our results showed that the 17-gene signature had a predictive prognostic value not only in single pathologic RCC, but also in multiple pathologic types of RCC. In conclusion, the 17-gene signature model was related to the survival of RCC patients and could help predict the prognosis with significant clinical implications.

scholarly journals Prognostic significance and immune correlates of CD73 expression in renal cell carcinoma

2020 ◽  
Vol 8 (2) ◽  
pp. e001467
Author(s):  
Abhishek Tripathi ◽  
Edwin Lin ◽  
Wanling Xie ◽  
Abdallah Flaifel ◽  
John A Steinharter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
T Cell ◽  
Protein Expression ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Significance ◽  
Cox Regression Analysis ◽  
Tcga Dataset ◽  
Cd73 Expression

BackgroundCD73–adenosine signaling in the tumor microenvironment is immunosuppressive and may be associated with aggressive renal cell carcinoma (RCC). We investigated the prognostic significance of CD73 protein expression in RCC leveraging nephrectomy samples. We also performed a complementary analysis using The Cancer Genome Atlas (TCGA) dataset to evaluate the correlation of CD73 (ecto-5′-nucleotidase (NT5E), CD39 (ectonucleoside triphosphate diphosphohydrolase 1 (ENTPD1)) and A2 adenosine receptor (A2AR; ADORA2A) transcript levels with markers of angiogenesis and antitumor immune response.MethodsPatients with RCC with available archived nephrectomy samples were eligible for inclusion. Tumor CD73 protein expression was assessed by immunohistochemistry and quantified using a combined score (CS: % positive cells×intensity). Samples were categorized as CD73negative (CS=0), CD73low or CD73high (< and ≥median CS, respectively). Multivariable Cox regression analysis compared disease-free survival (DFS) and overall survival (OS) between CD73 expression groups. In the TCGA dataset, samples were categorized as low, intermediate and high NT5E, ENTPD1 and ADORA2A gene expression groups. Gene expression signatures for infiltrating immune cells, angiogenesis, myeloid inflammation, and effector T-cell response were compared between NT5E, ENTPD1 and ADORA2A expression groups.ResultsAmong the 138 patients eligible for inclusion, ‘any’ CD73 expression was observed in 30% of primary tumor samples. High CD73 expression was more frequent in patients with M1 RCC (29% vs 12% M0), grade 4 tumors (27% vs 13% grade 3 vs 15% grades 1 and 2), advanced T-stage (≥T3: 22% vs T2: 19% vs T1: 12%) and tumors with sarcomatoid histology (50% vs 12%). In the M0 cohort (n=107), patients with CD73high tumor expression had significantly worse 5-year DFS (42%) and 10-year OS (22%) compared with those in the CD73negative group (DFS: 75%, adjusted HR: 2.7, 95% CI 1.3 to 5.9, p=0.01; OS: 64%, adjusted HR: 2.6, 95% CI 1.2 to 5.8, p=0.02) independent of tumor stage and grade. In the TCGA analysis, high NT5E expression was associated with significantly worse 5-year OS (p=0.008). NT5E and ENTPD1 expression correlated with higher regulatory T cell (Treg) signature, while ADORA2A expression was associated with increased Treg and angiogenesis signatures.ConclusionsHigh CD73 expression portends significantly worse survival outcomes independent of stage and grade. Our findings provide compelling support for targeting the immunosuppressive and proangiogenic CD73–adenosine pathway in RCC.

scholarly journals LRRK2 is a Candidate Prognostic Biomarker for Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Chunxiu Yang ◽  
Jingjing Pang ◽  
Jian Xu ◽  
He Pan ◽  
Yueying Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Bioinformatics Analysis ◽  
Clear Cell ◽  
Target Therapy ◽  
Prognostic Significance ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Gene Target

Abstract Background: Clear cell renal cell carcinoma (ccRCC), derived from renal tubular epithelial cells, is the most common malignant tumor of the kidney. The study of key genes related to the pathogenesis of ccRCC has become important for gene target therapy. Methods: Bioinformatics analysis of The Cancer Genome Atlas (TCGA) and the NCBI Gene Expression Omnibus (GEO) database were performed to examine the expression pattern and prognostic significance of leucine-rich repeat kinase 2 (LRRK2) expression and its relationship to clinical parameters. Immunohistochemistry and Western blot were performed to verify LRRK2 expression.Results: Bioinformatics analysis showed that LRRK2 expression was up-regulated in ccRCC, which was confirmed in ccRCC tissue immunohistochemically and by protein analysis. The level of expression was related to gender, pathological grade, stage and metastatic status of ccRCC patients. Meanwhile, Kaplan-Meier analysis showed that high expression of LRRK2 correlates to a better prognosis; protein-protein interaction network analysis showed that LRRK2 interacts with HIF1A and EGFR.Conclusion: We found that LRRK2 may play an important role in the tumorigenesis and progression of ccRCC. Our findings provided a potential predictor and therapeutic target in ccRCC.

A robust ferroptosis-related gene signature predicts overall survival in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Li Canxuan ◽  
Long Dan
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Risk Groups ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Entire Group ◽  
Cell Renal Cell Carcinoma

Aims: To investigate the prognostic values and potential mechanisms of ferroptosis-related genes in clear cell renal cell carcinoma. Methods: Univariate Cox, least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were employed to identify prognosis-related hub ferroptosis-related genes and establish a prognostic model. Results: The authors established a novel clinical predictive model based on seven hub ferroptosis-related genes in The Cancer Genome Atlas training cohort (n = 374) that was verified in the testing cohort (n = 156) and the entire group (n = 530). Functional analysis indicated that several carcinogenic pathways were enriched. Tumor-infiltrating cells and immunosuppressive molecules were significantly different between the two risk groups. Conclusion: Collectively, the authors successfully constructed a novel ferroptosis-related risk signature that was significantly associated with the prognosis of clear cell renal cell carcinoma.

scholarly journals DDX3X is Epigenetically Repressed in Renal Cell Carcinoma and Serves as a Prognostic Indicator and Therapeutic Target in Cancer Progression

2020 ◽  
Vol 21 (8) ◽  
pp. 2881
Author(s):  
Tsung-Chieh Lin
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Progression ◽  
Renal Cell ◽  
Biological Effects ◽  
The Cancer Genome Atlas ◽  
Prognostic Indicators ◽  
Rna Helicases ◽  
Poor Overall Survival ◽  
Expression Levels

DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) is a member of the DEAD-box family of RNA helicases whose function has been revealed to be involved in RNA metabolism. Recent studies further indicate the abnormal expression in pan-cancers and the relevant biological effects on modulating cancer progression. However, DDX3X’s role in renal cell carcinoma (RCC) progression remains largely unknown. In this study, a medical informatics-based analysis using The Cancer Genome Atlas (TCGA) dataset was performed to evaluate clinical prognoses related to DDX3X. The results suggest that DDX3X is epigenetically repressed in tumor tissue and that lower DDX3X is correlated with the poor overall survival of RCC patients and high tumor size, lymph node metastasis, and distant metastasis (TNM staging system). Furthermore, knowledge-based transcriptomic analysis by Ingenuity Pathway Analysis (IPA) revealed that the SPINK1-metallothionein pathway is a top 1-repressed canonical signaling pathway by DDX3X. Furthermore, SPINK1 and the metallothionein gene family all serve as poor prognostic indicators, and the expression levels of those genes are inversely correlated with DDX3X in RCC. Furthermore, digoxin was identified via Connectivity Map analysis (L1000) for its capability to reverse gene signatures in patients with low DDX3X. Importantly, cancer cell proliferation and migration were decreased upon digoxin treatment in RCC cells. The results of this study indicate the significance of the DDX3Xlow/SPINK1high/metallothioneinhigh axis for predicting poor survival outcome in RCC patients and suggest digoxin as a precise and personalized compound for curing those patients with low DDX3X expression levels.

Rare localization of renal cell carcinoma metastases in the paranasal sinuses and breast: a case report

2019 ◽  
Vol 22 (6) ◽  
pp. 13-22
Author(s):  
E. V. Kryaneva ◽  
N. A. Rubtsova ◽  
A. V. Levshakova ◽  
A. I. Khalimon ◽  
A. V. Leontyev ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Paranasal Sinuses ◽  
Renal Cell ◽  
Clinical Case ◽  
Clear Cell ◽  
Malignant Tumors ◽  
Metastatic Potential ◽  
Cell Renal Cell Carcinoma ◽  
Metastatic Lesions

This article presents a clinical case demonsratinga high metastatic potential of clear cell renal cell carcinoma combined with atypical metastases to breast and paranasal sinuses. The prevalence of metastatic lesions to the breast and paranasal sinuses in various malignant tumors depending on their morphological forms is analyzed. The authors present an analysis of data published for the last 30 years. The optimal diagnostic algorithms to detect the progression of renal cell carcinoma and to evaluate the effectiveness of the treatment are considered.

scholarly journals Low intratumor heterogeneity correlates with increased response to PD-1 blockade in renal cell carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097711
Author(s):  
Xia Ran ◽  
Jinyuan Xiao ◽  
Yi Zhang ◽  
Huajing Teng ◽  
Fang Cheng ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Simulated Data ◽  
The Cancer Genome Atlas ◽  
Intratumor Heterogeneity ◽  
Cell Renal Cell Carcinoma ◽  
Immune Activity

Background: Intratumor heterogeneity (ITH) has been shown to be inversely associated with immune infiltration in several cancers including clear cell renal cell carcinoma (ccRCC), but it remains unclear whether ITH is associated with response to immunotherapy (e.g. PD-1 blockade) in ccRCC. Methods: We quantified ITH using mutant-allele tumor heterogeneity, investigated the association of ITH with immune parameters in patients with ccRCC ( n = 336) as well as those with papillary RCC (pRCC, n = 280) from The Cancer Genome Atlas, and validations were conducted in patients with ccRCC from an independent cohort ( n = 152). The relationship between ITH and response to anti-PD-1 immunotherapy was explored in patients with metastatic ccRCC from a clinical trial of anti-PD-1 therapy ( n = 35), and validated in three equal-size simulated data sets ( n = 60) generated by random sampling with replacement based on this clinical trial cohort. Results: In ccRCC, low ITH was associated with better survival, more reductions in tumor burden, and clinical benefit of anti-PD-1 immunotherapy through modulating immune activity involving more neoantigens, elevated expression of HLA class I genes, and higher abundance of dendritic cells. Furthermore, we found that the association between the level of ITH and response to PD-1 blockade was independent of the mutation status of PBRM1 and that integrating both factors performed better than the individual predictors in predicting the benefit of anti-PD-1 immunotherapy in ccRCC patients. In pRCC, increased immune activity was also observed in low- versus high-ITH tumors, including higher neoantigen counts, increased abundance of monocytes, and decreased expression of PD-L1 and PD-L2. Conclusions: ITH may be helpful in the identification of patients who could benefit from PD-1 blockade in ccRCC, and even in pRCC where no genomic metrics has been found to correlate with response to immune checkpoint inhibitors.

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

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

scholarly journals Identification of Six Potentially Long Noncoding RNAs as Biomarkers Involved Competitive Endogenous RNA in Clear Cell Renal Cell Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Kang Yang ◽  
Xiao-fan Lu ◽  
Peng-cheng Luo ◽  
Jie Zhang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Cerna Network

Background. Clear cell renal cell carcinoma (ccRCC), the most common subtype of renal cell carcinoma (RCC), usually is representative of metastatic heterogeneous neoplasm that links with poor prognosis, but the pathogenesis of ccRCC remains unclear. Currently, numerous evidences prove that long noncoding RNAs (lncRNAs) are considered as competing endogenous RNA (ceRNA) to participate in cellular processes of tumors. Therefore, to investigate the underlying mechanisms of ccRCC, the expression profiles of lncRNAs, miRNAs, and mRNAs were downloaded from the Cancer Genome Atlas (TCGA) database. A total of 1526 differentially expressed lncRNAs (DElncRNAs), 54 DEmiRNAs, and 2352 DEmRNAs were identified. To determine the connection of them, all DElncRNAs were input to the miRcode database. The results indicated that 85 DElncRNAs could connect with 9 DEmiRNAs in relation to our study. Then, databases of TargetScan and miRDB were used to search for targeted genes with reference to DEmiRNAs. The results showed that 203 out of 2352 targeted genes were identified in our TCGA set. Subsequently, ceRNA network was constructed according to Cytoscape and the targeted genes were functionally analyzed to elucidate the mechanisms of DEmRNAs. The results of survival analysis and regression analysis indicated that 6 DElncRNAs named COL18A1-AS1, WT1-AS, LINC00443, TCL6, AL356356.1, and SLC25A5-AS1 were significantly correlative with the clinical traits of ccRCC patients and could be served as predictors for ccRCC. Finally, these findings were validated by quantitative RT-PCR (qRT-PCR). Based on these discoveries, we believe that this identified ceRNA network will provide a novel perspective to elucidate ccRCC pathogenesis.

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