scholarly journals TLR3 Serves as a Prognostic Biomarker and Associates with Immune Infiltration in the Renal Clear Cell Carcinoma Microenvironment

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Guodong Liao ◽  
Jia Lv ◽  
Alin Ji ◽  
Shuai Meng ◽  
Chao Chen
Keyword(s):  
T Cells ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Positive Association ◽  
Renal Clear Cell Carcinoma ◽  
Signalling Pathway ◽  
Poor Overall Survival ◽  
Immune Infiltration ◽  
Tlr3 Expression

Background. Clear cell renal cancer (KIRC) is one of the most common cancers globally, with a poor prognosis. TLRs play a vital role in anticancer immunity and the regulation of the biological progress of tumour cells. However, the precise role of TLRs in KIRC is still ambiguous. Methods. Various bioinformatics analysis and clinical validation of tissues were performed to evaluate the prognostic value of TLRs and their correlation with immune infiltration in KIRC. Results. The expression of TLR2/3/7/8 was increased at both mRNA and protein levels in KIRC. TLRs in KIRC were involved in the activation of apoptosis, EMT, RAS/MAPK, and RTK pathways, as well as the inhibition of the cell cycle and the hormone AR pathway. Drug sensitivity analysis revealed that high expression of TLR3 and low expression of TLR7/9/10 were resistant to most of the small molecules or drugs from CTRP. Enrichment analyses showed that TLRs were mainly involved in innate immune response, toll-like receptor signalling pathway, NF-kappa B signalling pathway, and TNF signalling pathway. Furthermore, a high-level TLR3 expression was associated with a favourable prognosis in KIRC. Validation research further confirmed that TLR3 expression was increased in KIRC tissues, and high TLR3 levels were associated with poor overall survival. Moreover, TLR3 in KIRC showed a positive association with an abundance of immune cells, including B-cells, CD4+ T-cells, CD8+ T-cells, macrophage, neutrophils, and dendritic cells, and the expression of the immune biomarker sets. Several TLR3-associated kinase, miRNA, or transcription factor targets were also identified in KIRC. Conclusion. Our results indicate that TLR3 serves as a prognostic biomarker and associated with immune infiltration in KIRC. This work lays a foundation for further studies on the role of TLR3 in the carcinogenesis and progression of KIRC.

scholarly journals Pseudogene HSPA7 is a Poor Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) and Correlated With Immune Infiltrates

2021 ◽  
Author(s):  
Chunjin Ding ◽  
Rundong He ◽  
Jinghan Zhang ◽  
Zhan Dong ◽  
Jun Wu
Keyword(s):  
Cox Regression ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Renal Clear Cell Carcinoma ◽  
Database Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
Infiltrating Cells ◽  
Cox Analysis

Abstract Background: Pseudogenes played important roles in tumorigenesis, while there are nearly no reports about the expression and roles of HSPA7 in the cancer. Methods: Firstly,we used Logistic regression,the KS test, the GEPIA database, UALCAN database and qRT-PCR to analyze the level of HSPA7 expressed in KIRC,then we used the Cox regression and the Kaplan-Meier curve to analyze the overall survival(OS) of KIRC patients with different Clinico-pathological parameters. Thirdly, we used the multivariate Cox analysis of influencing factors to compare the correlation between the HSPA7 expression level and the clinical parameters. Finally, we used multi-GSEA analysis and the Tumor Immunoassay Resource (TIMER) database to explore the functional role of HSPA7 in KIRC. Results: The HSPA7 is highly expressed in KIRC tumor tissues, and its expression is related to clinico-pathological features and survival in KIRCpatints.GSEA analysis displayed the high expression of HSPA7 in KIRC were related to several tumor-related and immune-related pathways. With the TIMER database analysis we showed that HSPA7 levels were correlated with the CD4+ T cells, neutrophils and Dendritic Cell.Conclusions: Our study showed that HSPA7 is very important in the tumor progression and may act as a poor prognostic biomarker for KIRC tumor by modulating immune infiltrating cells.

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.

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 Identification a ceRNA (XIST/miR-10a-5p/SERPINE1) Axis as a Prognostic Biomarker in Kidney Renal Clear Cell Carcinoma.

2021 ◽  
Author(s):  
Rui-ji Liu ◽  
Zhi-Peng Xu ◽  
Shuying Li ◽  
Jun-Jie Yu ◽  
Bin Xu ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Carcinoma ◽  
Immune Cell ◽  
Clear Cell ◽  
Prognostic Biomarker ◽  
Clear Cell Carcinoma ◽  
Renal Clear Cell Carcinoma ◽  
Immune Cell Infiltration ◽  
Cerna Network

Abstract Background: Kidney cancer is one of the most common malignancies, of which the most aggressive subtype was kidney renal clear cell carcinoma (KIRC), accounting for 80% of them. A growing number of studies point to the involvement of competitive endogenous RNAs in tumor development. However, the role of ceRNA network involved in KIRC remains unclear. Thus, the aim of this study was to investigate the BAP1-associated prognostic ceRNA in KIRC. Methods: We downloaded the RNAseq data from TCGA along with the relevant clinical data. We screened the differentially expressed lncRNAs, miRNAs, mRNAs according to the expression of BAP1 and established a ceRNA network. Results: After comprehensive bioinformatics analysis, we identified the XIST-miR-10a-5p-SERPINE1 ceRNA axis. Next, we confirmed the prognostic role of miR-10a-5p/SERPINE1 in KIRC using survival analysis and Cox regression analysis. To investigate the abnormally high expression of SERPINE1, we performed methylation analysis of SERPINE1 and concluded that the methylation level of SERPINE1 in KIRC was significantly lower than that in normal tissues. Furthermore, to study the role of SERPINE1 in the immune microenvironment in KIRC, we performed immune cell infiltration analysis and found that SERPINE1 expression was positively correlated with the level of multiple immune cell infiltration (CD 4+ T cell, CD 8+ T cell, macrophages, dendritic cells, neutrophils). Conclusion: We constructed a ceRNA (XIST/has-miR-10a-5p/SERPINE1) that can be used as prognostic biomarker of KIRC. Furthermore, we found that miR-10a-5p/SERPINE1 were significantly associated with clinical features and were independent prognostic factors of KIRC.

scholarly journals ACE2 Is a Prognostic Biomarker and Associated with Immune Infiltration in Kidney Renal Clear Cell Carcinoma: Implication for COVID-19

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Xinhao Niu ◽  
Zhe Zhu ◽  
Enming Shao ◽  
Juan Bao
Keyword(s):  
Immune Cells ◽  
Prognostic Biomarker ◽  
Enrichment Analysis ◽  
Tumor Grade ◽  
Renal Clear Cell Carcinoma ◽  
Cancer Stage ◽  
Immune Infiltration ◽  
Immunoglobulin Binding ◽  
Cancerous Cells

Background. KIRC is one of the most common cancers with a poor prognosis. ACE2 was involved in tumor angiogenesis and progression in many malignancies. The role of ACE2 in KIRC is still ambiguous. Methods. Various bioinformatics analysis tools were investigated to evaluate the prognostic value of ACE2 and its association with immune infiltration in KIRC. Results. ACE2 was shown to be downregulated in KIRC at the mRNA and protein level. Low expression of ACE2 protein in KIRC patients was observed in subgroup analyses based on gender, age, weight, tumor grade, and cancer stage. Upregulation of ACE2 in KIRC was associated with a favorable prognosis. ACE2 mRNA expression showed a positive correlation with the abundance of immune cells (B cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells) and the level of immune markers of different immune cells in KIRC. ACE2 expression could affect, in part, the immune infiltration and the advanced cancer stage. Moreover, enrichment analysis revealed that ACE2 in KIRC were mainly involved in translation factor activity, immunoglobulin binding, metabolic pathways, transcriptional misregulation in cancerous cells, cell cycle, and ribosomal activity. Several ACE2-associated kinases, miRNA, and transcription factor targets in KIRC were also identified. Conclusion. ACE2 was downregulated in KIRC and served as a prognostic biomarker. It was also shown to be associated with immune infiltration.

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 The role of FoxP3+ regulatory T cells and IDO+ immune and tumor cells in malignant melanoma – an immunohistochemical study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Satu Salmi ◽  
Anton Lin ◽  
Benjamin Hirschovits-Gerz ◽  
Mari Valkonen ◽  
Niina Aaltonen ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Factors ◽  
Regulatory T Cells ◽  
Tumor Cells ◽  
Immune Cells ◽  
Positive Association ◽  
Tumor Stage ◽  
Melanoma Cells ◽  
Melanoma Progression

Abstract Background FoxP3+ Regulatory T cells (Tregs) and indoleamine-2,3-dioxygenase (IDO) participate in the formation of an immunosuppressive tumor microenvironment (TME) in malignant cutaneous melanoma (CM). Recent studies have reported that IDO expression correlates with poor prognosis and greater Breslow’s depth, but results concerning the role of FoxP3+ Tregs in CM have been controversial. Furthermore, the correlation between IDO and Tregs has not been substantially studied in CM, although IDO is known to be an important regulator of Tregs activity. Methods We investigated the associations of FoxP3+ Tregs, IDO+ tumor cells and IDO+ stromal immune cells with tumor stage, prognostic factors and survival in CM. FoxP3 and IDO were immunohistochemically stained from 29 benign and 29 dysplastic nevi, 18 in situ -melanomas, 48 superficial and 62 deep melanomas and 67 lymph node metastases (LNMs) of CM. The number of FoxP3+ Tregs and IDO+ stromal immune cells, and the coverage and intensity of IDO+ tumor cells were analysed. Results The number of FoxP3+ Tregs and IDO+ stromal immune cells were significantly higher in malignant melanomas compared with benign lesions. The increased expression of IDO in melanoma cells was associated with poor prognostic factors, such as recurrence, nodular growth pattern and increased mitotic count. Furthermore, the expression of IDO in melanoma cells was associated with reduced recurrence˗free survival. We further showed that there was a positive correlation between IDO+ tumor cells and FoxP3+ Tregs. Conclusions These results indicate that IDO is strongly involved in melanoma progression. FoxP3+ Tregs also seems to contribute to the immunosuppressive TME in CM, but their significance in melanoma progression remains unclear. The positive association of FoxP3+ Tregs with IDO+ melanoma cells, but not with IDO+ stromal immune cells, indicates a complex interaction between IDO and Tregs in CM, which demands further studies.

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