scholarly journals YTHDF2 is a Potential Biomarker and Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Ganglin Su ◽  
Tianshu Liu ◽  
Xiaohong Han ◽  
Hao Sun ◽  
Wenan Che ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Rna Degradation ◽  
Renal Clear Cell Carcinoma ◽  
Mrna Transcription ◽  
Cell Renal Cell Carcinoma ◽  
Rna Molecules ◽  
Immune Infiltration ◽  
Potential Biomarker

Clear cell renal cell carcinoma (ccRCC or KIRC) has a high mortality rate globally. It is necessary to identify biomarkers and investigate the mechanisms those biomarkers are associated with, to improve the prognosis of patients with KIRC. N6-Methyladenosine (m6A) affects the fate of modified RNA molecules and is involved in tumor progression. Different webservers were used in our research to investigate the mRNA transcription and clinical significance of YTHDF2 in KIRC. Survival analysis revealed that patients with elevated YTHDF2 transcription had a slightly longer OS and DFS than those with low YTHDF2 expression. YTHDF2 expression was shown to be significantly associated with the abundance of immune cells such as B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. For a series of enrichment studies, we combined information on YTHDF2-binding molecules and expression-linked genes and identified the possible influence of “mRNA surveillance pathway,” “RNA degradation,” and “RNA transport” in the biology or pathogeny of KIRC. In addition, we identified multiple miRNA, kinase, and transcription factor targets of YTHDF2 in KIRC and constructed target networks. Overall, our findings show that YTHDF2 is a possible indicator of immune infiltration in the KIRC.

scholarly journals Prognostic Impact of MITD1 and Associates With Immune Infiltration in Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 20 ◽  
pp. 153303382110362
Author(s):  
Chujie Chen ◽  
Yiyu Sheng
Keyword(s):  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Disease Free Survival ◽  
Renal Clear Cell Carcinoma ◽  
Functional Enrichment ◽  
Prognostic Impact ◽  
Clinical Value ◽  
Immune Infiltration ◽  
Potential Biomarker

Kidney renal clear cell carcinoma (KIRC) is one of the most malignant diseases with poor survival rate over the world. The tumor microenvironment (TME) is highly related to the oncogenesis, development, and prognosis of KIRC. Thus, making the identification of KIRC biomarkers and immune infiltrates critically important. Microtubule Interacting and Trafficking Domain containing 1(MITD1) was reported to participate in cytokinesis of cell division. In the present study, multiple bioinformatics tools and databases were applied to investigate the expression level and clinical value of MITD1 in KIRC. We found that the expression of MITD1 was significantly increased in KIRC tissues. Further, the KIRC patients with high MITD1 levels showed a worse overall survival (OS) rate and disease free survival (DFS) rate. Otherwise, we found a significant correlation MITD1 expression and the abundance of CD8+ T cells. Functional enrichment analyses revealed that immune response and cytokine-cytokine receptor are very critical signaling pathways which associated with MITD1 in KIRC. In conclusion, our findings indicated that MITD1 may be a potential biomarker and associated with immune infiltration in KIRC.

scholarly journals A Novel Nine Apoptosis-Related Genes Signature Predicting Overall Survival for Kidney Renal Clear Cell Carcinoma and its Associations with Immune Infiltration

2021 ◽  
Vol 8 ◽  
Author(s):  
Yi Wang ◽  
Yinhao Chen ◽  
Bingye Zhu ◽  
Limin Ma ◽  
Qianwei Xing
Keyword(s):  
Overall Survival ◽  
Cell Carcinoma ◽  
Prognostic Model ◽  
Cox Regression ◽  
Clear Cell ◽  
Roc Curves ◽  
Renal Clear Cell Carcinoma ◽  
The Cancer Genome Atlas ◽  
Cell Renal Cell Carcinoma ◽  
Immune Infiltration

Background: This study was designed to establish a sensitive prognostic model based on apoptosis-related genes to predict overall survival (OS) in patients with clear cell renal cell carcinoma (ccRCC).Methods: Obtaining the expression of apoptosis-related genes and associated clinical parameters from online datasets (The Cancer Genome Atlas, TCGA), their biological function analyses were performed through differently expressed genes. By means of LASSO, unadjusted and adjusted Cox regression analyses, this predictive signature was constructed and validated by internal and external databases (both TCGA and ArrayExpress).Results: A total of nine apoptosis-related genes (SLC27A2, TNFAIP2, IFI44, CSF2, IL4, MDK, DOCK8, WNT5A, APP) were ultimately screened as associated hub genes and utilized to construct a prognosis model. Then our constructed riskScore model significantly passed the validation in both the internal and external datasets of OS (all p < 0.05) and verified their expressions by qRT-PCR. Moreover, we conducted the Receiver Operating Characteristic (ROC), finding the area under the ROC curves (AUCs) were all above 0.70 which indicated that riskScore was a stable independent prognostic factor (p < 0.05). Furthermore, prognostic nomograms were established to figure out the relationship between 1-, 3- and 5-year OS and individual parameters for ccRCC patients. Additionally, survival analyses indicated that our riskScore worked well in predicting OS in subgroups of age, gender, grade, stage, T, M, N0, White (all p < 0.05), except for African, Asian and N1 (p > 0.05). We also explored its association with immune infiltration and applied cMap database to seek out highly correlated small molecule drugs.Conclusion: Our study successfully constructed a prognostic model containing nine hub apoptosis-related genes for ccRCC, helping clinicians predict patients’ OS and making the prognostic assessment more standardized. Future prospective studies are required to validate our findings.

scholarly journals Antioxidant Gene Signature Impacts the Immune Infiltration and Predicts the Prognosis of Kidney Renal Clear Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueting Ren ◽  
Li Ma ◽  
Nan Wang ◽  
Ruina Zhou ◽  
Jianhua Wu ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Cell Carcinoma ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Gene Signature ◽  
Renal Clear Cell Carcinoma ◽  
Low Risk ◽  
Antioxidant Gene ◽  
Immune Infiltration

Background: Oxidative stress is related to oncogenic transformation in kidney renal clear cell carcinoma (KIRC). We intended to identify a prognostic antioxidant gene signature and investigate its relationship with immune infiltration in KIRC.Methods: With the support of The Cancer Genome Atlas (TCGA) database, we researched the gene expression and clinical data of KIRC patients. Antioxidant related genes with significant differences in expression between KIRC and normal samples were then identified. Through univariate and multivariate Cox analysis, a prognostic gene model was established and all patients were divided into high- and low-risk subgroups. Single sample gene set enrichment analysis was adopted to analyze the immune infiltration, HLA expression, and immune checkpoint genes in different risk groups. Finally, the prognostic nomogram model was established and evaluated.Results: We identified six antioxidant genes significantly correlated with the outcome of KIRC patients as independent predictors, namely DPEP1 (HR = 0.97, P < 0.05), GSTM3 (HR = 0.97, P < 0.05), IYD (HR = 0.33, P < 0.05), KDM3B (HR = 0.96, P < 0.05), PRDX2 (HR = 0.99, P < 0.05), and PRXL2A (HR = 0.96, P < 0.05). The high- and low-risk subgroups of KIRC patients were grouped according to the six-gene signature. Patients with higher risk scores had poorer prognosis, more advanced grade and stage, and more abundance of M0 macrophages, regulatory T cells, and follicular helper T cells. There were statistically significant differences in HLA and checkpoint gene expression between the two risk subgroups. The performance of the nomogram was favorable (concordance index = 0.766) and reliably predicted the 3-year (AUC = 0.792) and 5-year (AUC = 0.766) survival of patients with KIRC.Conclusion: The novel six antioxidant related gene signature could effectively forecast the prognosis of patients with KIRC, supply insights into the interaction between cellular antioxidant mechanisms and cancer, and is an innovative tool for selecting potential patients and targets for immunotherapy.

Tumor infiltrating and peripheral CD4+ILT2+ T cells are a cytotoxic subset selectively inhibited by HLA-G in clear cell renal cell carcinoma patients

2021 ◽  
Author(s):  
Alix Jacquier ◽  
Tiphaine Lambert ◽  
Jean-François Delattre ◽  
Malika Djouadou ◽  
Jérôme Vérine ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

Tumor-infiltrating CD8+ T cells recognize a heterogeneously expressed functional neoantigen in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Masahiro Matsuki ◽  
Yoshihiko Hirohashi ◽  
Munehide Nakatsugawa ◽  
Aiko Murai ◽  
Terufumi Kubo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Determinants of anti-PD1 response and resistance in clear cell renal cell carcinoma

2021 ◽  
Author(s):  
Lewis Au ◽  
Emine Hatipoglu ◽  
Marc Robert de Massy ◽  
Kevin Litchfield ◽  
Andrew Rowan ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Cd8 T Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Cell Renal Cell Carcinoma ◽  
Pre Treatment

Antigen recognition and T-cell mediated cytotoxicity in clear-cell renal cell carcinoma (ccRCC) remains incompletely understood. To address this knowledge gap, we analysed 115 multiregion tumour samples collected from 15 treatment-naive patients pre- and post-nivolumab therapy, and at autopsy in three patients. We performed whole-exome sequencing, RNAseq, TCRseq, multiplex immunofluorescence and flow cytometry analyses and correlated with clinical response. We observed pre-treatment intratumoural TCR clonal expansions suggesting pre-existing immunity. Nivolumab maintained pre-treatment expanded, clustered TCR clones in responders, suggesting ongoing antigen-driven stimulation of T-cells. T-cells in responders were enriched for expanded TCF7+CD8+ T-cells and upregulated GZMK/B upon nivolumab-binding. By contrast, nivolumab promoted accumulation of new TCR clones in non-responders, replacing pre-treatment expanded clonotypes. In this dataset, mutational features did not correlate with response to nivolumab and human endogenous retrovirus expression correlated indirectly. Our data suggests that nivolumab potentiates clinical responses in ccRCC by binding pre-existing expanded CD8+ T-cells to enhance cytotoxicity.

scholarly journals Genomic Landscape of Chinese Clear Cell Renal Cell Carcinoma Patients With Venous Tumor Thrombus Identifies Chromosome 9 and 14 Deletions and Related Immunosuppressive Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Shaoxi Niu ◽  
Kan Liu ◽  
Yong Xu ◽  
Cheng Peng ◽  
Yao Yu ◽  
...  
Keyword(s):  
T Cells ◽  
Cell Carcinoma ◽  
Primary Tumor ◽  
Clear Cell ◽  
Chromosome 9 ◽  
Genetic Profile ◽  
Copy Number Loss ◽  
Cell Renal Cell Carcinoma ◽  
Immunosuppressive Microenvironment ◽  
Matched Primary Tumor

BackgroundClear cell renal cell carcinoma (ccRCC) with venous tumor thrombus (VTT) is associated with a poor clinical outcome. Although several studies have examined the genomic features of ccRCC, the genetic profile of VTT along with its matched primary tumor has not been fully elucidated.Materials and methodsSamples of VTT tissues and matched primary tumor tissues from ccRCC patients (n = 25), as well as primary tumor tissues from patients without VTT (n = 25) were collected and analyzed using whole-exome sequencing. Four additional ccRCC patients who were unfit for surgery were treated with an anti-programmed death receptor-1 (PD-1) monoclonal antibody (Toripalimab, 240 mg, Q3W, IV).ResultsBy comparing the primary kidney tumors from ccRCC patients with or without VTT, a relatively higher prevalence of BAP1 and KDM5C alterations were found in ccRCC patients with VTT, and these alterations were associated with worse overall survival in the kidney renal clear cell carcinoma (KIRC) database. Based on subclone analysis, VTT was predicted to primarily originate directly from the primary renal mass. A significantly higher prevalence of CELSR2 and TET2 alterations were identified in the VTTs compared with the matched primary tumors. An increased prevalence of DNA damage repair genes, especially those involved in homologous recombination repair and non-homologous end joining, was found in ccRCC patients with VTT. Notably, VTT was characterized by the increase incidence of copy number loss in the whole exome (p < 0.05), particularly in the chromosome 9 and 14 regions. Deletion of chromosome 9 and 14 was associated with worse survival, unfavorable clinical features, and the presence of an immunosuppressive microenvironment, which was characterized by higher infiltration of regulatory T cells, follicular helper T cells, and resting mast cells, but lower counts of resting CD4 memory T cells and CD8 positive T cells. A significantly lower count of CD4+ and CD8+ tumor-infiltrated lymphocytes was identified in the VTT samples comparing with matched primary tumor. Of note, three out of the four ccRCC patients with VTT in our cohort who were treated with the anti-PD-1 therapy exhibited remarkable remission in the renal mass but no notable shrinkage in the VTT mass.ConclusionOur study revealed the genetic profile of Chinese ccRCC patients with VTT, and identified multiple features associated with known poor outcomes, including gene alterations and copy number loss. The deletions in chromosomes 9 and 14, and the associated immunosuppressive microenvironment may indicate limited sensitivity to anti-PD-1/PD-L1 monotherapy in VTT.

Systematic Analyses of The Role of Prognostic And Immunological of EIF3A, A Reader Protein, In Clear Cell Renal Cell Carcinoma

2021 ◽  
Author(s):  
Yi Zhang ◽  
Xiaoliang Hua ◽  
Haoqiang Shi ◽  
Li Zhang ◽  
HaiBing Xiao ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cells ◽  
Cell Carcinoma ◽  
Immune Cells ◽  
Renal Cell ◽  
Clear Cell ◽  
Multivariate Analyses ◽  
Enrichment Analysis ◽  
Marker Genes ◽  
Cell Renal Cell Carcinoma

Abstract Background: Eukaryotic initiation factor 3a, EIF3A, as a “reader” protein for RNA methylation, has been found to be related to promote tumorigenesis in different variety of cancers. The impaction of EIF3A in clear cell renal cell carcinoma (ccRCC) has yet to be expounded. This study aimed to identify the prognostic value of EIF3A in ccRCC and investigate the relationship between expression and immune infiltration.Methods: We collected 29 m6a related mRNA data and clinicopathological parameters from Cancer Genmoe Atlas (TCGA) database. Logistic regression analyses were used to analyze the correlation between EIF3A expression and clinical characteristics. Immunohistochemistry (IHC) were applied to examine EIF3A levels in normal and ccRCC tissues. Univariate and multivariate analyses were conducted to recognize forcefully independent factor in associated with overall survival (OS) and diseases free survival (DFS). Nomogram was aim at predicting the 1-, 3-and 5-year survival probabilities. Gene set enrichment analysis (GSEA) was carried out to the potential function and related signaling pathways of EIF3A expression. To investigate EIF3A of co-expressed genes, we used LinkedOmics and its result was undertaken enrichment analysis. Simultaneously, to employ LinkedOmics and STRING dataset drew a conclusion that EIF3A co-expressed genes and visualized via Cytoscape. Finally, we evaluated that EIF3A expression correlated between with infiltration of immune cells and the expression of marker genes in ccRCC by Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA).Result: EIF3A expression was significantly different between ccRCC tissues and normal tissues. EIF3A expression was connected with poor prognostic clinicopathological factors, and K–M analyses revealed that low EIF3A expression was correlated with poor prognosis. The result of univariate and multivariate analyses proved that EIF3A was a prognostic factor in ccRCC patients. GSEA results indicated that high expression was enriched in renal cell carcinoma pathway and so on. EIF3A expression was significantly positively correlated with B cells, CD8+T cells, CD4+T cells, neutrophils, macrophages, and dendritic cells. Furthermore, EIF3A expression was associated with most of marker genes of immune cells.Conclusions: EIF3A could serve as potential biomarkers for prognostic and diagnostic stratification factor for ccRCC and is related with immune cells infiltrates.

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