scholarly journals Neo-Fs Index: A Novel Immunohistochemical Biomarker Panel Predicts Survival and Response to Anti-Angiogenetic Agents in Clear Cell Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1199
Author(s):  
Jisup Kim ◽  
Jee-Young Park ◽  
Su-Jin Shin ◽  
Beom Jin Lim ◽  
Heounjeong Go
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Plasmacytoid Dendritic Cell ◽  
Cytolytic Activity ◽  
Immune Gene ◽  
Protein Markers ◽  
Cell Renal Cell Carcinoma ◽  
Frameshift Indels

Background: Frameshift indels have emerged as a predictor of immunotherapy response but were not evaluated yet to predict anti-angiogenetic agent (AAA) response or prognosis in clear cell renal cell carcinoma (ccRCC). Methods: Here, to develop biomarkers that predict survival and response to AAA, we evaluated the immunohistochemical expression of proteins whose genes frequently harbor frameshift indels in 638 ccRCC patients and correlated the individual and integrated markers with prognosis and AAA response. The mutational landscape was evaluated using targeted next-generation sequencing in 12 patients concerning protein markers. Immune gene signatures were retrieved from TCGA RNA seq data. Results: Five proteins (APC, NOTCH1, ARID1A, EYS, and filamin A) were independent adverse prognosticators and were incorporated into the Neo-fs index. Better overall, disease-specific and recurrence-free survival were observed with high Neo-fs index in univariate and multivariate survival analyses. Better AAA responses were observed with a high Neo-fs index, which reflected increased MHC class I, CD8+ T cell, cytolytic activity, and plasmacytoid dendritic cell signatures and decreased type II-IFN response signatures, as well as greater single-nucleotide variant (SNV) and indel counts. Conclusions: Neo-fs index, reflecting antitumor immune signature and more SNVs. and indels, is a powerful predictor of survival and AAA response in ccRCC.

TFE3-PD-L1 axis is pivotal for sunitinib resistance in clear cell renal cell carcinoma

2020 ◽  
Author(s):  
Xudong Guo ◽  
Ruxia Li ◽  
Qiulei Bai ◽  
Shaobo Jiang ◽  
Hanbo Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Mouse Model ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Nuclear Translocation ◽  
Clear Cell ◽  
Chromosomal Translocation ◽  
Cytolytic Activity ◽  
Cell Renal Cell Carcinoma ◽  
Western Blots

Abstract Background: The microphthalmia of bHLH-LZ transcription factors (MiT/TFE) family chromosomal translocation or overexpression is linked with a poor prognosis in clear cell renal cell carcinoma (ccRCC) with elevated recurrence and drug resistance, but the molecular mechanism is not fully understood. Here, we investigated whether the resistance to sunitinib malate (Sun), the standard treatment for metastatic RCC, is due to upregulation of programmed death ligand 1 (PD-L1) by the transcription factor E3 (TFE3) in ccRCC.Methods: The effect of TFE3 expression on ccRCC proliferation had been evaluated. The regulation of TFE3 on PD-L1 was assessed by qPCR and western blots in human primary clear cell lines and ccRCC specimens. The regulation of Sun on TFE3 and PD-L1 was assessed by western blots and flow cytometry. The therapeutic efficacy of Sun plus PD-L1 blockade was evaluated in xenograft mouse model.Results: In this study, we propose that TFE3 but not TFEB is essential for tumor survival and more importantly it is more of a promotor of cell proliferation which was associated with the poorer survival of cancer patients. We also found a positive correlation between TFE3 and PD-L1 expression in clear cell RCC cells and tissues. Sun treatment led to enhanced TFE3 nuclear translocation and PD-L1 expression. Finally, we observed the therapeutic benefit of Sun plus PD-L1 inhibition which enhanced CD8+ cytolytic activity and thus tumor suppression in a xenografted mouse model.Conclusions: Our data provides a strong rationale to apply Sun and PD-L1 inhibition jointly as a novel immunotherapeutic approach for ccRCC treatment.

scholarly journals Development of an Individualized Immune Prognostic Signature for Clear Cell Renal Cell Carcinoma through the Identification of Differential Immune Genes

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jianfeng Wang ◽  
Chaozhi Tang ◽  
Xiaowu Liu
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Immune Gene ◽  
Cell Renal Cell Carcinoma ◽  
Immune Genes ◽  
Tumor Microenvironments ◽  
Prognosis Model

Increasing evidence has shown that tumor microenvironments are an important feature in clear cell renal cell carcinoma (ccRCC) carcinogenesis and therapeutic efficacy. In this study, two subtypes of ccRCC, high- and low-immune groups, were identified based on the immune gene datasets, of which the differential immune genes were identified accordingly. Furthermore, we constructed a risk prognosis model using five immune genes, specifically, AQP9, KIAA1429, HAMP, CCL13, and CCL21. This model was highly predictive of ccRCC clinical characteristics and showed potential for use in immunotherapy. Furthermore, the five identified genes were highly correlated with the abundance of B cells, CD4 T cells, CD8 T cells, macrophages, neutrophils, and dendritic cells in the tumor microenvironments. Among them, AQP9, KIAA1429, and HAMP exhibited significant prognostic potential. These findings indicate that monitoring and operating tumor microenvironments are of great significance for ccRCC prognosis and precise immunotherapy.

Immunohistochemical Analysis of Prognostic Protein Markers for Primary Localized Clear Cell Renal Cell Carcinoma

2013 ◽  
Vol 31 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Thomas Weber ◽  
Matthias Meinhardt ◽  
Stefan Zastrow ◽  
Andreas Wienke ◽  
Susanne Fuessel ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Immunohistochemical Analysis ◽  
Protein Markers ◽  
Cell Renal Cell Carcinoma

scholarly journals Review of Prognostic Expression Markers for Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Florent Petitprez ◽  
Mira Ayadi ◽  
Aurélien de Reyniès ◽  
Wolf H. Fridman ◽  
Catherine Sautès-Fridman ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clinical Utility ◽  
Prognostic Markers ◽  
Clear Cell ◽  
Evidence Synthesis ◽  
Protein Markers ◽  
Cell Renal Cell Carcinoma ◽  
Pubmed Database

Context: The number of prognostic markers for clear cell renal cell carcinoma (ccRCC) has been increasing regularly over the last 15 years, without being integrated and compared.Objective: Our goal was to perform a review of prognostic markers for ccRCC to lay the ground for their use in the clinics.Evidence Acquisition: PubMed database was searched to identify RNA and protein markers whose expression level was reported as associated with survival of ccRCC patients. Relevant studies were selected through cross-reading by two readers.Evidence Synthesis: We selected 249 studies reporting an association with prognostic of either single markers or multiple-marker models. Altogether, these studies were based on a total of 341 distinct markers and 13 multiple-marker models. Twenty percent of these markers were involved in four biological pathways altered in ccRCC: cell cycle, angiogenesis, hypoxia, and immune response. The main genes (VHL, PBRM1, BAP1, and SETD2) involved in ccRCC carcinogenesis are not the most relevant for assessing survival.Conclusion: Among single markers, the most validated markers were KI67, BIRC5, TP53, CXCR4, and CA9. Of the multiple-marker models, the most famous model, ClearCode34, has been highly validated on several independent datasets, but its clinical utility has not yet been investigated.Patient Summary: Over the years, the prognosis studies have evolved from single markers to multiple-marker models. Our review highlights the highly validated prognostic markers and multiple-marker models and discusses their clinical utility for better therapeutic care.

scholarly journals Significance of Tumor Mutation Burden Related Immune Gene in the Progression and Prognosis of Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Zhirong Yang ◽  
Duo Yun ◽  
Longmei Dai ◽  
Qinqin Wang ◽  
Xiangli Guo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Common Mutation ◽  
Immune Gene ◽  
Cell Renal Cell Carcinoma ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
The Relationship

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is a common renal malignant disease with a poor prognosis. There were limited studies focus on the relationship between Tumor mutation burden (TMB) and ccRCC.Methods: Based on TCGA-ccRCC cohort, we summarized the status of gene mutations in ccRCC. Then, we analyzed the relationship between TMB and clinical characteristic. Meanwhile, we identified some TMB-related immune genes through the intersection of TMB-Related differentially expressed genes (DEGs) and immune related genes. Finally, we selected the highest correction and novel genes for the future analysis.Results: The most common mutation of Variant Classification, Variant Type, SNV Class were missense mutations, SNP, C>T, respectively. Higher TMB related to shorter overall survival (OS), lower age and grade. Finally, we identified PAEP gene, a novel TMB-related immune gene in ccRCC, which was significantly overexpression in ccRCC tissues and cells with progression and poor survival in ccRCC patients. Furthermore, PAEP promoted the invasion, migration, and proliferation of ccRCC cells. Mechanistically, PAEP suppressed the PI3K/Akt/NF-κB signaling pathway.Conclusion: Our study suggests that PAEP might represents a potential target of antibody immunotherapy for ccRCC patients.

638: Macroscopic Tumor Necrosis is a Prognostic Indicator for Non-Metastatic Clear Cell Renal Cell Carcinoma

2007 ◽  
Vol 177 (4S) ◽  
pp. 214-214
Author(s):  
Sung Kyu Hong ◽  
Byung Kyu Han ◽  
In Ho Chang ◽  
June Hyun Han ◽  
Ji Hyung Yu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Necrosis ◽  
Clear Cell ◽  
Prognostic Indicator ◽  
Cell Renal Cell Carcinoma ◽  
Macroscopic Tumor

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.

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