scholarly journals Protocadherin17 Promoter Methylation is a Potential Predictive Biomarker in Clear Cell Renal Cell Carcinoma

2015 ◽  
Vol 21 ◽  
pp. 2870-2876 ◽  
Author(s):  
Ying-Li Lin ◽  
Shi-Liang Gui ◽  
Hong Guo ◽  
Jian-Guo Ma ◽  
Wen-Ping Li
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Promoter Methylation ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarker ◽  
Cell Renal Cell Carcinoma

scholarly journals Long Noncoding RNA HOTTIP Serves as an Independent Predictive Biomarker for the Prognosis of Patients with Clear Cell Renal Cell Carcinoma

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Zhanxin Liu ◽  
Zichun Wang ◽  
Xiaoxiong Wang ◽  
Meisong Lu ◽  
Guang Chen
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Noncoding Rna ◽  
Clear Cell ◽  
Clinical Stage ◽  
Predictive Biomarker ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Advanced Clinical Stage

Several studies have indicated that HOXA transcript at the distal tip (HOTTIP) play important roles in the tumorigenesis and development of various cancers. We aim to investigate the expression and prognostic value of HOTTIP in clear cell renal cell carcinoma (ccRCC). A systematic review of PubMed, Embase, Medline, and Web of Science databases was performed to select eligible literatures relevant to the correlation between HOTTIP expression and clinical outcome of different cancers. The association between the HOTTIP level and overall survival (OS), lymph node metastasis (LNM), or clinical stage was subsequently analyzed. Survival analyses were performed in a large cohort of more than 500 patients with ccRCC from The Cancer Genome Atlas (TCGA) using bioinformatic methods. Seventeen studies with a total of 1594 patients with thirteen kinds of carcinomas were included in this analysis. The result showed that high HOTTIP expression could predict worse outcome in cancer patients, with the pooled hazard ratio (HR) of 2.34 (95% confidence interval (CI) 1.96–2.79, p<0.0001). The result also showed that elevated HOTTIP expression was correlated with more LNM (OR=2.61, 95% CI 1.91-3.58, p<0.0001) and advanced clinical stage (OR=3.57, 95% CI 2.58-4.93, p<0.0001). We further validated that ccRCC patients with higher HOTTIP expression tend to have unsatisfactory outcomes both in the entire TCGA dataset and different clinical stratums, like age, grade, and stage. The tumor of those patients was associated with a larger size, easier to metastasis, advanced clinical stage, and a higher pathological grade. These findings suggested that increased HOTTIP expression might act as a novel prognostic marker for ccRCC patients.

scholarly journals EVI1 as a Prognostic and Predictive Biomarker of Clear Cell Renal Cell Carcinoma

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 300 ◽  
Author(s):  
Luis Palomero ◽  
Lubomir Bodnar ◽  
Francesca Mateo ◽  
Carmen Herranz-Ors ◽  
Roderic Espín ◽  
...  
Keyword(s):  
Gene Expression ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Transcriptional Control ◽  
Clear Cell ◽  
Predictive Biomarker ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Immunohistochemical Studies

The transcription factor EVI1 plays an oncogenic role in several types of neoplasms by promoting aggressive cancer features. EVI1 contributes to epigenetic regulation and transcriptional control, and its overexpression has been associated with enhanced PI3K-AKT-mTOR signaling in some settings. These observations raise the possibility that EVI1 influences the prognosis and everolimus-based therapy outcome of clear cell renal cell carcinoma (ccRCC). Here, gene expression and protein immunohistochemical studies of ccRCC show that EVI1 overexpression is associated with advanced disease features and with poorer outcome—particularly in the CC-e.3 subtype defined by The Cancer Genome Atlas. Overexpression of an oncogenic EVI1 isoform in RCC cell lines confers substantial resistance to everolimus. The EVI1 rs1344555 genetic variant is associated with poorer survival and greater progression of metastatic ccRCC patients treated with everolimus. This study leads us to propose that evaluation of EVI1 protein or gene expression, and of EVI1 genetic variants may help improve estimates of prognosis and the benefit of everolimus-based therapy in ccRCC.

scholarly journals Validation of VEGFR1 rs9582036 as predictive biomarker in metastatic clear-cell renal cell carcinoma patients treated with sunitinib

2016 ◽  
Vol 118 (6) ◽  
pp. 890-901 ◽  
Author(s):  
Benoit Beuselinck ◽  
Johnny Jean-Baptiste ◽  
Patrick Schöffski ◽  
Gabrielle Couchy ◽  
Clément Meiller ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarker ◽  
Cell Renal Cell Carcinoma

Carbonic Anhydrase IX As a Predictive Biomarker for Clear Cell Renal Cell Carcinoma

2008 ◽  
Vol 26 (18) ◽  
pp. 3105-3107 ◽  
Author(s):  
Allan J. Pantuck ◽  
Tobias Klatte ◽  
David Seligson ◽  
Michael Atkins ◽  
Arie Belldegrun
Keyword(s):  
Renal Cell Carcinoma ◽  
Carbonic Anhydrase ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarker ◽  
Carbonic Anhydrase Ix ◽  
Cell Renal Cell Carcinoma

scholarly journals BRCA1-Associated Protein 1 (BAP-1) as a Prognostic and Predictive Biomarker in Clear Cell Renal Cell Carcinoma: A Systematic Review

Kidney Cancer ◽  
2021 ◽  
pp. 1-13
Author(s):  
Shuchi Gulati ◽  
Melissa Previtera ◽  
Maria F. Czyzyk-Krzeska ◽  
Primo Nery Lara
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarker ◽  
Cell Renal Cell Carcinoma ◽  
Thymic Epithelial Tumors

BACKGROUND: The gene that encodes BRCA1-associated protein 1 (BAP1) has been reported to be dysregulated in several human cancers such as uveal melanoma, malignant pleural mesothelioma, hepatocellular carcinoma, thymic epithelial tumors, and clear-cell renal cell carcinoma (ccRCC). The gene is located on the human chromosome 3p21.3, encoding a deubiquitinase and acts as a classic two-hit tumor suppressor gene. BAP1 predominantly resides in the nucleus, where it interacts with several chromatin-associated factors, as well as regulates calcium signaling in the cytoplasm. As newer therapies continue to evolve for the management of RCC, it is important to understand the role of BAP1 mutation as a prognostic and predictive biomarker. OBJECTIVE: We aimed to systematically evaluate the role of BAP1 mutations in patients with RCC in terms of its impact on prognosis and its role as a predictive biomarker. METHODS: Following PRISMA guidelines, we performed a systematic literature search using PubMed and Embase through March 2021. Titles and abstracts were screened to identify articles for full-text and then a descriptive review was performed. RESULTS: A total of 490 articles were initially identified. Ultimately 71 articles that met our inclusion criteria published between 2012–2021 were included in the analysis. Data were extracted and organized to reflect the role of BAP1 alterations as a marker of prognosis as well as a marker of response to treatments, such as mTOR inhibitors, VEGF tyrosine kinase inhibitors, and immune checkpoint inhibitors. CONCLUSIONS: Alterations in BAP1 appear to be uniformly associated with poor prognosis in patients with RCC. Knowledge gaps remain with regard to the predictive relevance of BAP1 alterations, especially in the context of immunotherapy. Prospective studies are required to more precisely ascertain the predictive value of BAP1 alterations in RCC.

scholarly journals Identification of clear cell renal cell carcinoma and oncocytoma using a three-gene promoter methylation panel

2017 ◽  
Vol 15 (1) ◽  
Author(s):  
Ana Sílvia Pires-Luís ◽  
Pedro Costa-Pinheiro ◽  
Maria João Ferreira ◽  
Luís Antunes ◽  
Francisco Lobo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Promoter Methylation ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Promoter ◽  
Cell Renal Cell Carcinoma

scholarly journals Promoter methylation inhibits expression of tumor suppressor KIBRA in human clear cell renal cell carcinoma

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Katrin Schelleckes ◽  
Boris Schmitz ◽  
Giuliano Ciarimboli ◽  
Malte Lenders ◽  
Hermann J. Pavenstädt ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Promoter Methylation ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals CTLA4 promoter hypomethylation is a negative prognostic biomarker at initial diagnosis but predicts response and favorable outcome to anti-PD-1 based immunotherapy in clear cell renal cell carcinoma

2021 ◽  
Vol 9 (8) ◽  
pp. e002949
Author(s):  
Niklas Klümper ◽  
Damian J Ralser ◽  
Romina Zarbl ◽  
Katrin Schlack ◽  
Andres Jan Schrader ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Mrna Expression ◽  
Renal Cell ◽  
Clear Cell ◽  
Predictive Biomarker ◽  
Initial Diagnosis ◽  
First Line ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

BackgroundIn metastatic clear cell renal cell carcinoma (ccRCC), different combination therapies, each including anti-PD-1 immune checkpoint blockade (ICB), are applied as first-line treatment. Robust predictive biomarkers for rational upfront therapy decisions are lacking, although they are urgently needed. Recently, we showed that CTLA4 promoter methylation predicts response to ICB in melanoma. Here, we aimed to investigate CTLA4 methylation in ccRCC and its utility to serve as a predictive biomarker for anti-PD-1 based ICB in metastatic ccRCC.MethodsCTLA4 methylation was analyzed with regard to transcriptional gene activity (mRNA expression), intratumoral immune cell composition, and clinical course in two ccRCC cohorts obtained from The Cancer Genome Atlas (TCGA cohort, n=533) and the University Hospital Bonn (UHB Non-ICB Cohort, n=116). In addition, CTLA4 methylation as well as CD8+ T cell infiltrates and PD-L1 expression were evaluated in pre-treatment samples from a multicenter cohort (RCC-ICB Cohort, n=71). Patients included in the RCC-ICB Cohort were treated with either first line anti-PD-1 based combination therapy (n=25) or monotherapy post–tyrosine kinase inhibition in second line or later. Analyses were performed with regard to treatment response according to RECIST, progression-free survival (PFS), event-free survival (EFS), and overall survival (OS) following treatment initiation.ResultsCTLA4 promoter hypomethylation was significantly correlated with CTLA4 mRNA expression, lymphocyte infiltration, and poor OS in both primary ccRCC cohorts (TCGA: HR 0.30 (95% CI 0.18 to 0.49), p<0.001; UHB Non-ICB: HR 0.35 (95% CI 0.16 to 0.75), p=0.007). In contrast, CTLA4 promoter hypomethylation predicted response and, accordingly, favorable outcomes (PFS and OS) in patients with ICB-treated ccRCC, overcompensating the negative prognostic value of CTLA4 hypomethylation at initial diagnosis. Moreover, in multivariable Cox regression, CTLA4 promoter hypomethylation remained an independent predictor of improved outcome in ICB-treated ccRCC after co-adjustment of the International Metastatic Renal Cell Carcinoma Database Consortium score (HR 3.00 (95% CI 1.47 to 6.28), p=0.003).ConclusionsOur study suggests CTLA4 methylation as a powerful predictive biomarker for immunotherapy response in metastatic RCC.

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