scholarly journals Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 667 ◽  
Author(s):  
Gorka Larrinaga ◽  
Jon Danel Solano-Iturri ◽  
Peio Errarte ◽  
Miguel Unda ◽  
Ana Loizaga-Iriarte ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Cell Cancer ◽  
Tissue Expression ◽  
Cell Renal Cell Carcinoma ◽  
Tumor Center

(1). Background: Immunohistochemical (IHC) evaluation of programmed death-1 (PD-1) and its ligand (PD-L1) is being used to evaluate advanced malignancies with potential response to immune checkpoint inhibitors. We evaluated both plasma and tissue expression of PD-1 and PD-L1 in the same cohort of patients, including non-metastatic and metastatic clear cell renal cell carcinoma (CCRCC). Concomitant plasma and tissue expression of PD-1 and PD-L1 was evaluated with emphasis on diagnostic and prognostic implications. (2) Methods: we analyzed PD-1 and PD-L1 IHC expression in tumor tissues and soluble forms (sPD-1 and sPD-L1) in plasma from 89 patients with CCRCC, of which 23 were metastatic and 16 received systemic therapy. The primary endpoint was evaluation of overall survival using Kaplan-Meier analysis and the Cox regression model. Plasma samples from healthy volunteers were also evaluated. (3) Results: Interestingly, sPD-1 and sPD-L1 levels were lower in cancer patients than in controls. sPD-1 and sPD-L1 levels and their counterpart tissue expression both at the tumor center and infiltrating front were not associated. Higher expression of both PD-1 and PD-L1 were associated with tumor grade, necrosis and tumor size. PD-1 was associated to tumor stage (pT) and PD-L1 to metastases. sPD-1 and sPD-L1 were not associated with clinico-pathological parameters, although both were higher in patients with synchronous metastases compared to metachronous ones and sPD-L1 was also higher for metastatic patients compared to non-metastatic patients. sPD-1 was also associated with the International Metastatic Renal Cell Cancer Database Consortium (IMDC) prognostic groups in metastatic CCRCC and also to the Morphology, Attenuation, Size and Structure (MASS) response criteria in metastatic patients treated with systemic therapy, mainly tyrosine-kinase inhibitors. Regarding prognosis, PD-L1 immunostaining at the tumor center with and without the tumor front was associated with worse survival, and so was sPD-L1 at a cut-off >793 ng/mL. Combination of positivity at both the tissue and plasma level increased the level of significance to predict prognosis. (4) Conclusions: Our findings corroborate the role of PD-L1 IHC to evaluate prognosis in CCRCC and present novel data on the usefulness of plasma sPD-L1 as a promising biomarker of survival in this neoplasia.

scholarly journals A novel 10 glycolysis-related genes signature could predict overall survival for clear cell renal cell carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qianwei Xing ◽  
Tengyue Zeng ◽  
Shouyong Liu ◽  
Hong Cheng ◽  
Limin Ma ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Low Risk ◽  
The Cancer Genome Atlas ◽  
Regression Analyses ◽  
Cell Renal Cell Carcinoma

Abstract Background The role of glycolysis in tumorigenesis has received increasing attention and multiple glycolysis-related genes (GRGs) have been proven to be associated with tumor metastasis. Hence, we aimed to construct a prognostic signature based on GRGs for clear cell renal cell carcinoma (ccRCC) and to explore its relationships with immune infiltration. Methods Clinical information and RNA-sequencing data of ccRCC were obtained from The Cancer Genome Atlas (TCGA) and ArrayExpress datasets. Key GRGs were finally selected through univariate COX, LASSO and multivariate COX regression analyses. External and internal verifications were further carried out to verify our established signature. Results Finally, 10 GRGs including ANKZF1, CD44, CHST6, HS6ST2, IDUA, KIF20A, NDST3, PLOD2, VCAN, FBP1 were selected out and utilized to establish a novel signature. Compared with the low-risk group, ccRCC patients in high-risk groups showed a lower overall survival (OS) rate (P = 5.548Ee-13) and its AUCs based on our established signature were all above 0.70. Univariate/multivariate Cox regression analyses further proved that this signature could serve as an independent prognostic factor (all P < 0.05). Moreover, prognostic nomograms were also created to find out the associations between the established signature, clinical factors and OS for ccRCC in both the TCGA and ArrayExpress cohorts. All results remained consistent after external and internal verification. Besides, nine out of 21 tumor-infiltrating immune cells (TIICs) were highly related to high- and low- risk ccRCC patients stratified by our established signature. Conclusions A novel signature based on 10 prognostic GRGs was successfully established and verified externally and internally for predicting OS of ccRCC, helping clinicians better and more intuitively predict patients’ survival.

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

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.

scholarly journals Prognostic Value of DNA Methylation-Driven Genes in Clear Cell Renal Cell Carcinoma: A Study Based on Methylation and Transcriptome Analyses

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Maolin Hu ◽  
Jiangling Xie ◽  
Huiming Hou ◽  
Ming Liu ◽  
Jianye Wang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Risk Score ◽  
Renal Cell ◽  
Methylation Level ◽  
Cox Regression ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

Background. Few previous studies have comprehensively explored the level of DNA methylation and gene expression in ccRCC. The purpose of this study was to identify the key clear cell renal cell carcinoma- (ccRCC-) related DNA methylation-driven genes (MDG) and to build a prognostic model based on the level of DNA methylation. Methods. RNA-seq transcriptome data and DNA methylation data were obtained from The Cancer Genome Atlas. Based on the MethylMix algorithm, we obtain ccRCC-related MDG. The univariate and multivariate Cox regression analyses were employed to investigate the correlation between patient overall survival and the methylation level of each MDG. Finally, a prognosis risk score was established based on a linear combination of the regression coefficient derived from the multivariate Cox regression model (β) multiplied with the methylation level of the gene. Results. 19 ccRCC-related MDG were identified. Three MDG (NCKAP1L, EVI2A, and BATF) were further screened and integrated into a prognostic risk score model, risk score=3.710∗methylation level of NCKAP1L+−3.892∗methylation level of EVI2A+−3.907∗methylation level of BATF. The risk model was independent from conventional clinical characteristics as a prognostic factor for ccRCC (HR=1.221, 95% confidence interval: 1.063–1.402, and P=0.005). The joint survival analysis showed that the gene expression and methylation levels of the prognostic genes EVI2A and BATF were significantly related with prognosis. Conclusion. This study provided an important bioinformatics foundation for in-depth studies of ccRCC DNA methylation.

Response to systemic therapy in non-clear cell renal cell carcinomas: A systematic review and meta-analysis.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 425-425 ◽  
Author(s):  
Francisco Emilio Vera-Badillo ◽  
Arnoud Templeton ◽  
Alberto Ocana ◽  
Paulo deGouveia ◽  
Priya Aneja ◽  
...  
Keyword(s):  
Systematic Review ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Clear Cell ◽  
Meta Analysis ◽  
Cell Renal Cell Carcinoma

425 Background: Clinical data supporting the efficacy of systemic therapy in non-clear cell renal cell carcinoma (non-ccRCC) are limited and based on retrospective analyses, expanded access programs and single arm phase II trials. Therefore the optimal treatment for this subgroup remains uncertain. Methods: A systematic review of electronic databases was conducted to identify publications evaluating the outcomes of patients with non-ccRCC (excluding those with sarcomatoid tumors) treated with different systemic approaches (immunotherapy, chemotherapy, targeted agents, small molecules). The primary endpoint was response rate and secondary endpoints were median progression free (PFS) and overall survival (OS). Where possible, data were pooled in a meta-analysis using the Mantel-Haenszel random-effect modeling. For studies comprising of unselected patients, outcomes of those with non-ccRCC were compared with clear cell renal cell carcinoma (ccRCC). Results: Forty-nine studies comprising 7,799 patients were included: 471 patients were enrolled on studies conducted exclusively in non-ccRCC and 7,328 patients on studies of unselected renal cell carcinoma. Among these, 903 (12%) had non-ccRCC and 6,425 (88%) had ccRCC. For non-ccRCC, overall response rate, median PFS and median OS were 9%, 7.9 and 13.4 months, respectively. By comparison, the overall response rate for ccRCC was 15% (Risk Ratio for response [RR] 0.67, 95% CI 0.52-0.86, p=0.002). This association was independent of type of treatment administered. Among the different novel agents (bevacizumab, lenalidomide, linefanib, sorafenib, sunitinib, pazopanib, everolimus and temsirolimus), sunitinib was significantly less efficacious in non-ccRCC than ccRCC (RR 0.56, 95% CI 0.42-0.72), but there was no significant difference in response rates for sorafenib (RR 0.64, 95% CI 0.31-1.35) or other agents (RR 1.10, 95% CI 0.50-2.44), However, confidence intervals were wide. Results of further analyses will be presented at the meeting. Conclusions: Patients with non-ccRCC have lower response rates than those with ccRCC, but the absolute difference between them is modest. Further study of targeted therapy in non-ccRCC is warranted.

STAT-3 and Β-catenin expression in metastatic clear cell renal cell carcinoma (mRCC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 583-583
Author(s):  
Aline Fusco Fares ◽  
Isabela Cunha ◽  
Daniel Vilarim Araujo ◽  
Leonardo de Azevedo Boente ◽  
Daniel Garcia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Clear Cell ◽  
Antiangiogenic Therapy ◽  
Prognostic Scores ◽  
Cancer Center ◽  
Cell Renal Cell Carcinoma ◽  
Prognostic Criteria

583 Background: In mRCC, there are no prospectively validated biomarkers to guide the treatment and therapy decision is based on prognostic scores and histology. STAT-3 and Wnt/b-cateninare cell proliferation pathways and have already been related to prognostic in renal cell carcinoma. Objective: to evaluate the role of STAT-3 and b-catenin expression as prognostic biomarkers in clear cell mRCC. Methods: 684 medical records of renal cell carcinoma patients treated at AC Camargo Cancer Center from 2007 to 2015 were reviewed. 86 out of 684 patients fulfilled the study criteria: metastatic clear cell carcinoma, no sarcomatoid features, previous systemic therapy, previous nephrectomy and available tumor specimens from metastatic site. Pathological samples were arranged in a TMA. The number of positive stainings cells for each antibody in each core was categorized as low positive or negative versus highly positive expression. Results: We had available tissue blocks from 47 tumors. 32/45 patients (71,1%) had highly positive membrane b-catenin and none of the patients was positive for nuclear b-catenin. 27 /45 (60%) were categorized as low positive or negative STAT-3. There was no statistically significant association between STAT-3 and b-catenin expression with clinical prognostic criteria (MSKCC and Heng criteria). In the multivariate analysis, KPS < 80% (p = 0.02; HR: 2.7), time from nephrectomy to metastasis < 1 year (p = 0.04; HR: 2.1), no hypothyroidism (p = 0.05; HR: 2.4) and MSKCC criteria (p = 0.02; HR: 2.5) were confirmed as negative prognostic factors. Associative analysis showed that none of the patients with negative membrane b-catenin had response to systemic therapy (p=0.02). OS was 35.5 months (IC 22.2-48.8) and PFS was 12.5 months (IC 10.0-14.0). Conclusions: in our cohort, STAT-3 and B-catenin expression are not associated with the prognostic criteria (MSKCC and Heng). The loss of B-catenin expression is associated to a worse response rate to antiangiogenic therapy in metastatic clear cell renal cancer. [Table: see text]

scholarly journals A Novel Immune-Related lncRNA-Based Model for Survival Prediction in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-37
Author(s):  
Zedan Zhang ◽  
Yanlin Tang ◽  
Yanjun Liu ◽  
Hongkai Zhuang ◽  
Enyu Lin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clear Cell ◽  
Functional Enrichment ◽  
Clinical Parameters ◽  
Training Set ◽  
Cell Renal Cell Carcinoma

Background. Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer whose incidence and mortality rate are increasing. Identifying immune-related lncRNAs and constructing a model would probably provide new insights into biomarkers and immunotherapy for ccRCC and aid in the prognosis prediction. Methods. The transcription profile and clinical information were obtained from The Cancer Genome Atlas (TCGA). Immune-related gene sets and transcription factor genes were downloaded from GSEA website and Cistrome database, respectively. Tumor samples were divided into the training set and the testing set. Immune-related differentially expressed lncRNAs (IDElncRNAs) were identified from the whole set. Univariate Cox regression, LASSO, and stepwise multivariate Cox regression were performed to screen out ideal prognostic IDElncRNAs (PIDElncRNAs) from the training set and develop a multi-lncRNA signature. Results. Consequently, AC012236.1, AC078778.1, AC078950.1, AC087318.1, and AC092535.4 were screened to be significantly related to the prognosis of ccRCC patients, which were used to establish the five-lncRNA signature. Its wide diagnostic capacity was revealed in different subgroups of clinical parameters. Then AJCC-stage, Fuhrman-grade, pharmaceutical, age, and risk score regarded as independent prognostic factors were integrated to construct a nomogram, whose good performance in predicting 3-, 5-, and 7-year overall survival of ccRCC patients was revealed by time-dependent ROC curves and verified by the testing sets and ICGC dataset. The calibration plots showed great agreement of the nomogram between predicted and observed outcomes. Functional enrichment analysis showed the signature and each lncRNA were mainly enriched in pathways associated with regulation of immune response. Several kinds of tumor-infiltrating immune cells like regulatory T cells, T follicular helper cells, CD8+ T cells, resting mast cells, and naïve B cells were significantly correlated with the signature. Conclusion. Therefore, we constructed a five-lncRNA model integrating clinical parameters to help predict the prognosis of ccRCC patients. The five immune-related lncRNAs could potentially be therapeutic targets for immunotherapy in ccRCC in the future.

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 Metastatic Lesion of the Tibia from Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Piotr Młodożeniec ◽  
Krzysztof Balawender ◽  
Mateusz Zasadny
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Cancer ◽  
Local Therapy ◽  
X Rays ◽  
Cell Renal Cell Carcinoma ◽  
Lower Limb Pain

Introduction. Renal cell carcinoma is responsible for 3% of all cancers, with the highest incidence occurring in Western countries. Additionally, in patients with osseous metastasis, only 3% occur within the tibia. Rarely, a patient presents with a primary complaint of lower limb pain in advanced metastatic renal cell carcinoma. Case Presentation. The patient arrived at the emergency department with a primary complaint of left ankle pain. Ankle X-rays demonstrated a lytic lesion involving the medial malleolus with possible metastatic disease. CT scan confirmed a tumor within the right kidney. The patient was treated with a laparoscopic radical nephrectomy with histopathologic confirmation of clear cell renal cell carcinoma. Biopsy was then performed of the tibial lesion, confirming metastatic clear cell renal cell carcinoma. The tibial lesion was treated with local radiotherapy, and because of the progression of the tibia lesion, a decision was made to amputate the leg. Additionally, the patient was enrolled to sunitinib treatment and was disease free at one year of follow-up. 13 months after diagnosis of cancer, she was suffering a major stroke of the brain that caused her to die. Conclusion. The treatment of patients with osseous metastases of renal cell cancer depends on the number of metastases, location of metastases, and overall health of the patient. We performed an overview of available literature and provided a summary regarding the use of cytoreductive nephrectomy, local therapy, target therapy, and bone-targeting agents in the treatment of metastatic renal cell cancer.

MicroRNA-15a tissue expression is a prognostic marker for survival in patients with clear cell renal cell carcinoma

2019 ◽  
Vol 19 (4) ◽  
pp. 515-524 ◽  
Author(s):  
Yulian Mytsyk ◽  
Yuriy Borys ◽  
Lesia Tumanovska ◽  
Dmytro Stroy ◽  
Askold Kucher ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Prognostic Marker ◽  
Renal Cell ◽  
Clear Cell ◽  
Tissue Expression ◽  
Cell Renal Cell Carcinoma

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.

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