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

Author(s):  
Zhirong Yang ◽  
Duo Yun ◽  
Longmei Dai ◽  
Qinqin Wang ◽  
Xiangli Guo ◽  
...  

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.

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1199
Author(s):  
Jisup Kim ◽  
Jee-Young Park ◽  
Su-Jin Shin ◽  
Beom Jin Lim ◽  
Heounjeong Go

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.


2019 ◽  
Vol 72 (5) ◽  
pp. 354-362 ◽  
Author(s):  
Qin Jin ◽  
Yanfeng Dai ◽  
Yan Wang ◽  
Shu Zhang ◽  
Gang Liu

AimsKinesin family member 11 (Kif11) is a member of the kinesin family motor proteins, which is associated with spindle formation and tumour genesis. In this study, we investigated the relationship between Kif11 expression and clear cell renal cell carcinoma (CCRCC) development.MethodsThe relationship between Kif11 expression and CCRCC development was analysed by quantitative real-time (qRT)-PCR analyses, and tissue immunohistochemistry. The prognostic significance of Kif11 expression was explored by univariable and multivariable survival analyses of 143 included patients. Furthermore, SB743921 was used as a specific Kif11 inhibitor to treat 786-O cells with the epithelial to mesenchymal transition (EMT) process analysed by qRT-PCR, and cell survival rates analysed with Annexin V-FITC/PI staining followed by flow cytometric analyses. Disease-free survival curves of Kif11 with different cancers and the relationships between Kif11 and the von Hippel-Lindau disease tumour suppressor gene (VHL), and proliferating cell nuclear antigen (PCNA) in kidney cancer were further analysed using the GEPIA database.ResultsThe levels of Kif11 mRNA were significantly higher in CCRCC tissues compared with corresponding non-cancerous tissues. The results of immunohistochemistry demonstrated that the expression of Kif11 protein was significantly associated with clinicopathologial parameters, including nuclear grade and TNM stage. The Kaplan-Meier survival curve indicated that high Kif11 expression, nuclear grade and TNM stage were independent factors to predict poor prognosis in patients with CCRCC. In addition, inhibition of Kif11 expression by SB743921 suppressed cell proliferation, migration and the EMT process with increased apoptosis rate.ConclusionsThese results combined with bioinformation analyses suggest that high Kif11 expression was associated with unfavourable prognosis in CCRCC and could be used as a potential prognostic marker in the clinical diagnosis of CCRCC.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jianfeng Wang ◽  
Chaozhi Tang ◽  
Xiaowu Liu

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.


2007 ◽  
Vol 177 (4S) ◽  
pp. 214-214
Author(s):  
Sung Kyu Hong ◽  
Byung Kyu Han ◽  
In Ho Chang ◽  
June Hyun Han ◽  
Ji Hyung Yu ◽  
...  

2019 ◽  
Vol 22 (6) ◽  
pp. 13-22
Author(s):  
E. V. Kryaneva ◽  
N. A. Rubtsova ◽  
A. V. Levshakova ◽  
A. I. Khalimon ◽  
A. V. Leontyev ◽  
...  

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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