Leukotriene B4 receptor 2 correlates with prognosis and immune infiltration in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Xia Yuan ◽  
Yi He ◽  
Chenhui Luo ◽  
Wei Wang
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Leukotriene B4 ◽  
Cell Renal Cell Carcinoma ◽  
Immune Infiltration ◽  
Leukotriene B4 Receptor

scholarly journals Identification of Prognostic Metabolism-Related Genes in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yusa Chen ◽  
Yumei Liang ◽  
Ying Chen ◽  
Shaxi Ouyang ◽  
Kanghan Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Random Forest ◽  
Cell Carcinoma ◽  
Differentially Expressed Genes ◽  
Renal Cell ◽  
Multivariate Regression ◽  
Clinical Characteristics ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Immune Infiltration

Background. Clear cell renal cell carcinoma (ccRCC) is a cancer with abnormal metabolism. The purpose of this study was to investigate the effect of metabolism-related genes on the prognosis of ccRCC patients. Methods. The data of ccRCC patients were downloaded from the TCGA and the GEO databases and clustered using the nonnegative matrix factorization method. The limma software package was used to analyze differences in gene expression. A random forest model was used to screen for important genes. A novel Riskscore model was established using multivariate regression. The model was evaluated based on the metabolic pathway, immune infiltration, immune checkpoint, and clinical characteristics. Results. According to metabolism-related genes, kidney clear cell carcinoma (KIRC) datasets downloaded from TCGA were clustered into two groups and showed significant differences in prognosis and immune infiltration. There were 667 differentially expressed genes between the two clusters, of which 408 were screened by univariate analysis. Finally, 12 differentially expressed genes (MDK, SLC1A1, SGCB, C4orf3, MALAT1, PILRB, IGHG1, FZD1, IFITM1, MUC20, KRT80, and SALL1) were filtered out using the random forest model. The model of Riskscore was obtained by multiplying the expression levels of these 12 genes with the corresponding coefficients of the multivariate regression. We found that the Riskscore correlated with the expression of these 12 genes; the high Riskscore matched the low survival rate verified in the verification set. The analysis found that the Riskscore model was associated with most of the metabolic processes, immune infiltration of cells such as plasma cells, immune checkpoints such as PD-1, and clinical characteristics such as M stage. Conclusion. We established a new Riskscore model for the prognosis of ccRCC based on metabolism. The genes in the model provided several novel targets for the study of ccRCC.

scholarly journals Prognostic significance and tumor-immune infiltration of mTOR in clear cell renal cell carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11901
Author(s):  
Na Li ◽  
Jie Chen ◽  
Qiang Liu ◽  
Hongyi Qu ◽  
Xiaoqing Yang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Clinical Role ◽  
Cell Renal Cell Carcinoma ◽  
Cancer Specific Survival ◽  
Immune Infiltration

Mammalian target of rapamycin (mTOR), a serine/threonine kinase involved in cell proliferation, survival, metabolism and immunity, was reportedly activated in various cancers. However, the clinical role of mTOR in renal cell carcinoma (RCC) is controversial. Here we detected the expression and prognosis of total mTOR and phosphorylated mTOR (p-mTOR) in clear cell RCC (ccRCC) patients, and explored the interactions between mTOR and immune infiltrates in ccRCC. The protein level of mTOR and p-mTOR was determined by western blotting (WB), and their expression was evaluated in 145 ccRCC and 13 non-tumor specimens by immunohistochemistry (IHC). The relationship to immune infiltration of mTOR was further investigated using TIMER and TISIDB databases, respectively. WB demonstrated the ratio of p-mTOR to mTOR was higher in ccRCC than adjacent specimens (n = 3), and IHC analysis elucidated that p-mTOR expression was positively correlated with tumor size, stage and metastasis status, and negatively correlated with cancer-specific survival (CSS). In univariate analysis, high grade, large tumor, advanced stage, metastasis, and high p-mTOR expression were recognized as prognostic factors of poorer CSS, and multivariate survival analysis elucidated that tumor stage, p-mTOR and metastasis were of prognostic value for CSS in ccRCC patients. Further TIMER and TISIDB analyses uncovered that mTOR gene expression was significantly associated with numerous immune cells and immunoinhibitors in patients with ccRCC. Collectively, these findings revealed p-mTOR was identified as an independent predictor of poor survival, and mTOR was associated with tumor immune infiltrates in ccRCC patients, which validated mTOR could be implicated in the initiation and progression of ccRCC.

scholarly journals Prognostic Roles of Phosphofructokinase Platelet in Clear Cell Renal Cell Carcinoma and Correlation with Immune Infiltration

2021 ◽  
Vol Volume 14 ◽  
pp. 3645-3658
Author(s):  
Bin Liu ◽  
Faping Li ◽  
Mingdi Liu ◽  
Zhixiang Xu ◽  
Baoshan Gao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Immune Infiltration

scholarly journals Comprehensive Analysis of Ferroptosis Regulators With Regard to PD-L1 and Immune Infiltration in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Song Wang ◽  
Shiming Chen ◽  
Yufan Ying ◽  
Xueyou Ma ◽  
Haixiang Shen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Gene Set Enrichment Analysis ◽  
M2 Macrophage ◽  
Cell Renal Cell Carcinoma ◽  
Immune Infiltration ◽  
M1 Macrophage ◽  
Cluster 2

Clear cell renal cell carcinoma (ccRCC) is one of the tumor types with sensitivity to ferroptosis, and immunotherapy has emerged as a standard pillar for metastatic ccRCC treatment, while it remains largely obscure whether ferroptosis influences the tumor immune microenvironment in ccRCC. Based on available data in The Cancer Genome Atlas, divergent expression profiles of ferroptosis regulators were noted in ccRCC and normal tissues, and we also found that the ferroptosis regulators correlated with the PD-L1 expression. Two independent subtypes were determined by consensus clustering analysis according to the expression level of ferroptosis regulators in ccRCC. Cluster 1 showed lower histological tumor stage and grade, more favorable prognosis, and higher PD-L1 expression compared to cluster 2. CIBERSORT analysis revealed that cluster 2 harbored higher infiltrated levels of CD8+ T cell, Tregs, and T follicular helper cell, while cluster 1 more correlated with the monocyte, M1 macrophage, and M2 macrophage. Gene set enrichment analysis indicated that the ERBB signaling and JAK_STAT signaling pathways were significantly enriched in cluster 1. We subsequently identified CARS as the potentially key immune infiltration-related ferroptosis regulator, whose high expression showed dismal prognosis and was positively correlated with PD-L1 expression in ccRCC. We also verified the upregulation of CARS in ccRCC tissues and cell lines via qRT-PCR method. Additionally, a pan-cancer analysis demonstrated that CARS closely related to the expression of immune checkpoint-related genes (especially PD-L1) and an unfavorable prognosis in diverse cancer types. In summary, our study suggested the crucial role of ferroptosis in immune infiltration of ccRCC, and CARS is a potentially novel prognostic biomarker and potential target for cancer immunotherapy.

scholarly journals Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy

2021 ◽  
Vol 9 ◽  
Author(s):  
Peng Zhou ◽  
Yuchao Lu ◽  
Yang Xun ◽  
Jinzhou Xu ◽  
Chenqian Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Post Translational Modification ◽  
Sequencing Data ◽  
Cell Renal Cell Carcinoma ◽  
E3 Ligases ◽  
Assessment Protocol ◽  
Immune Infiltration

Ubiquitin modification is the most common protein post-translational modification (PTM) process in organisms, and 1332 ubiquitin regulators have been identified in humans. Ubiquitin regulators, especially E3 ligases and deubiquitinases, are widely involved in immune processes. This study aims to explore the ubiquitin modification features of clear cell renal cell carcinoma (ccRCC) and to elucidate the role of such ubiquitin modifications in shaping anti-tumor immunity and individual benefits from immune checkpoint blockade (ICB). A comprehensive analysis was performed in the TCGA cohort (n = 530) and GEO cohort (n = 682). RNA sequencing data of 758 differentially expressed regulators, which was validated by the proteomics data, was used for k-means unsupervised consensus clustering and three ubiquitin patterns of ccRCC were identified. Then, we focused on the ubiquitin modification and tumor progression signatures, immune infiltration characteristics, and prognostic value. The three patterns with different ubiquitin modification signatures correspond to “immune desert phenotype,” “immune resistance phenotype,” and “immune-inflammatory phenotype,” respectively. To facilitate clinical application, we constructed a ubiquitin score to evaluate individual patients’ ubiquitination outcome, and it was demonstrated to be an independent risk factor for overall survival (OS) in multivariate Cox analysis. It was found that the high score group was correlated to higher immune cells infiltrating level and PD-1/PD-L1/CTLA-4 expression. More importantly, we found that the high score group was predicted to be sensitive to anti-PD-1 treatment, while the low-score group showed lower predicted IC50 values in treatment with Pazopanib and Axitinib. In summary, this study elucidated the potential link between ubiquitin modification and immune infiltration landscape of ccRCC for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced ccRCC.

scholarly journals Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma

2020 ◽  
Vol 26 (6) ◽  
pp. 909-918 ◽  
Author(s):  
David A. Braun ◽  
Yue Hou ◽  
Ziad Bakouny ◽  
Miriam Ficial ◽  
Miriam Sant’ Angelo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Immune Infiltration ◽  
Somatic Alterations

scholarly journals GNRH1 and LTB4R might be novel immune-related prognostic biomarkers in clear cell renal cell carcinoma (ccRCC)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hua-Hui Wu ◽  
Xin Yan ◽  
Zhao Chen ◽  
Guo-Wei Du ◽  
Xiao-Jie Bai ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Leukotriene B4 ◽  
Gene Set Enrichment Analysis ◽  
Prognostic Biomarkers ◽  
Cell Renal Cell Carcinoma

Abstract Background Clear cell renal cell carcinoma (ccRCC) occupied most of renal cell carcinoma (RCC), which associated with poor prognosis. The purpose of this study is to screen novel and prognostic biomarkers for patients with ccRCC. Methods and results Firstly, Gene Expression Omnibus database was used to collect microarray data for weighted gene co-expression network construction. Gene modules related to prognosis which interest us most were picked out. 90 hub genes were further chosen in the key modules, two of which including gonadotropin releasing hormone 1 (GNRH1) and leukotriene B4 receptor (LTB4R) were screened and validated as immune-related prognostic biomarkers. Based on several public databases and ccRCC tissues collected by ourselves, we performed survival analysis, spearman correlation analysis, receiver operating characteristic (ROC) analysis, quantitative real-time PCR (qRT-PCR), western blotting, immunofluorescence (IF) and immunohistochemistry (IHC) staining for the validation of immune-related prognostic biomarkers. We further explored the relationship between immune-related prognostic biomarker expressions and immunocytes. Finally, gene set enrichment analysis (GSEA) demonstrated that the two immune-related prognostic biomarkers were significantly correlated with cell cycle. Conclusions Generally speaking, the present study has identified two novel prognostic biomarkers for patients with ccRCC, which showed strong correlation with prognosis of patients with ccRCC, could further be used as potential prognostic biomarkers in ccRCC.

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