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 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 Overexpressed pseudogene MT1L associated with tumor immune infiltrates and indicates a worse prognosis in BLCA

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yanpeng Ding ◽  
Nuomin Liu ◽  
Mengge Chen ◽  
Yulian Xu ◽  
Sha Fang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Biological Function ◽  
Prognostic Biomarker ◽  
Poor Survival ◽  
Common Cancer ◽  
Kaplan Meier ◽  
Cox Analysis ◽  
Kaplan Meier Plotter ◽  
Worse Prognosis

Abstract Background BLCA is a common cancer worldwide, and it is both aggressive and fatal. Immunotherapy (ICT) has achieved an excellent curative effect in BLCA; however, only some BLCA patients can benefit from ICT. MT1L is a pseudogene, and a previous study suggested that MT1L can be used as an indicator of prognosis in colorectal cancer. However, the role of MT1L in BLCA has not yet been determined. Methods Data were collected from TCGA, and logistic regression, Kaplan-Meier plotter, and multivariate Cox analysis were performed to demonstrate the correlation between the pseudogene MT1L and the prognosis of BLCA. To identify the association of MT1L with tumor-infiltrating immune cells, TIMER and TISIDB were utilized. Additionally, GSEA was performed to elucidate the potential biological function. Results The expression of MT1L was decreased in BLCA. Additionally, MT1L was positively correlated with immune cells, such as Tregs (ρ = 0.708) and MDSCs (ρ = 0.664). We also confirmed that MT1L is related to typical markers of immune cells, such as PD-1 and CTLA-4. In addition, a high MT1L expression level was associated with the advanced T and N and high grade in BLCA. Increased expression of MT1L was significantly associated with shorter OS times of BLCA patients (p < 0.05). Multivariate Cox analysis revealed that MT1L expression could be an independent prognostic factor in BLCA. Conclusion Collectively, our findings demonstrated that the pseudogene MT1L regulates the immune microenvironment, correlates with poor survival, and is an independent prognostic biomarker in BLCA.

scholarly journals High Expression of PRMT6 Associated With Prognosis and Immune Infiltration in Glioma

2020 ◽  
Author(s):  
Yi Yang ◽  
Zhenshuang Wang ◽  
Shengrong Long ◽  
Jinhai Huang ◽  
Chengran Xu ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Clinical Work ◽  
High Expression ◽  
Clinical Indicators ◽  
Immune Infiltration ◽  
Tumor Tissues ◽  
Potential Biomarker ◽  
Patient Prognosis ◽  
The Relationship

Abstract Background: Gliomas are characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, with the increase of grade, the prognosis of glioma is increasingly poor and not optimistic. Therefore, biological markers for glioma are needed in clinical work, which can be utilized to detect and evaluate the situation and prognosis of glioma patients. Many studies have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors and is associated with patient prognosis. However, the role of PRMT6 in glioma has not been reported or analyzed. Methods: In this study, we used a variety of tumor related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from the perspective of bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. In addition, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from the perspectives of mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results: PRMT6 is significantly differentially expressed in a variety of tumors and is associated with survival and prognosis. Especially in gliomas, the expression of PRMT6 gradually increased with the increase of grade. In addition, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in a variety of databases. Conclusions: Our results indicate that high expression of PRMT6 is a potential biomarker for predicting glioma prognosis and progression.

scholarly journals Prognostic and immunological value of LTB4R in pan-cancer

2021 ◽  
Vol 18 (6) ◽  
pp. 9336-9356
Author(s):  
Sidan Long ◽  
◽  
Shuangshuang Ji ◽  
Kunmin Xiao ◽  
Peng Xue ◽  
...  
Keyword(s):  
Immune Cells ◽  
Prognostic Significance ◽  
Enrichment Analysis ◽  
Negative Influence ◽  
Leukotriene B4 ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Immune Infiltration ◽  
Significant Difference ◽  
Pan Cancer

<abstract> <sec><title>Background</title><p>LTB4 receptor 1 (LTB4R), as the high affinity leukotriene B4 receptor, is rapidly revealing its function in malignancies. However, it is still uncertain.</p> </sec> <sec><title>Methods</title><p>We investigated the expression pattern and prognostic significance of LTB4R in pan-cancer across different databases, including ONCOMINE, PrognoScan, GEPIA, and Kaplan-Meier Plotter, in this study. Meanwhile, we explored the significance of LTB4R in tumor metastasis by HCMDB. Then functional enrichment analysis of related genes was performed using GeneMANIA and DAVID. Lastly, utilizing the TIMER datasets, we looked into the links between LTB4R expression and immune infiltration in malignancies.</p> </sec> <sec><title>Results</title><p>In general, tumor tissue displayed higher levels of LTB4R expression than normal tissue. Although LTB4R had a negative influence on pan-cancer, a high expression level of LTB4R was protective of LIHC (liver hepatocellular carcinoma) patients' survival. There was no significant difference in the distribution of LTB4R between non-metastatic and metastatic tumors. Based on Gene Set Enrichment Analysis, LTB4R was implicated in pathways involved in inflammation, immunity, metabolism, and cancer diseases. The correlation between immune cells and LTB4R was found to be distinct across cancer types. Furthermore, markers of infiltrating immune cells, such as Treg, T cell exhaustion and T helper cells, exhibited different LTB4R-related immune infiltration patterns.</p> </sec> <sec><title>Conclusion</title><p>The LTB4R is associated with immune infiltrates and can be used as a prognostic biomarker in pan-cancer.</p> </sec> </abstract>

scholarly journals CTHRC1 expression is a novel shared diagnostic and prognostic biomarker of survival in six different human cancer subtypes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nuzhat Sial ◽  
Mukhtiar Ahmad ◽  
Muhammad Safdar Hussain ◽  
Muhammad Junaid Iqbal ◽  
Yasir Hameed ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Prognostic Biomarker ◽  
Human Cancer ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Renal Clear Cell Carcinoma ◽  
Clinicopathological Features ◽  
Cancer Subtypes ◽  
Normal Tissues ◽  
Collagen Triple Helix

AbstractAccording to the previous reports, the collagen triple helix repeat containing 1 (CTHRC1) causes tumorigenesis by modulating the tumor microenvironment, however, the evidence is limited to a few human cancer subtypes. In the current study, we analyzed and validated the CTHRC1 expression variations in 24 different human cancer tissues paired with normal tissues using publically available databases. We observed that CTHRC1 was overexpressed in all the 24 major subtypes of human cancers and its overexpression was significantly associated with the reduced overall survival (OS) duration of head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), liver hepatocellular carcinoma (LIHC), Lung adenocarcinoma (LUAD), stomach adenocarcinoma (STAD), and Uterine corpus endometrial carcinoma (UCEC). This implies that CTHRC1 plays a significant role in the development and progression of these cancers. We further noticed that CTHRC1 was also overexpressed in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features. Pathways enrichment analysis revealed the involvement of CTHRC1 associated genes in seven diverse pathways. We also explored few interesting correlations between CTHRC1 expression and promoter methylation, genetic alterations, CNVs, CD8+ T immune cells infiltration, and tumor purity. In conclusion, CTHRC1 can serve as a shared diagnostic and prognostic biomarker in HNSC, KIRC, LIHC, LUAD, STAD, and UCEC patients of different clinicopathological features.

scholarly journals Identification of potential therapeutic targets for atherosclerosis by analysing the gene signature related to different immune cells and immune regulators in atheromatous plaques

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yang Shen ◽  
Li-rong Xu ◽  
Xiao Tang ◽  
Chang-po Lin ◽  
Dong Yan ◽  
...  
Keyword(s):  
Immune Cells ◽  
Plasma Cells ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gamma Delta ◽  
Hub Genes ◽  
Gene Set Enrichment ◽  
Bioinformatics Analyses ◽  
Immune Infiltration ◽  
Atheromatous Plaques

Abstract Background Atherosclerosis is a chronic inflammatory disease that affects multiple arteries. Numerous studies have shown the inherent immune diversity in atheromatous plaques and suggest that the dysfunction of different immune cells plays an important role in atherosclerosis. However, few comprehensive bioinformatics analyses have investigated the potential coordinators that might orchestrate different immune cells to exacerbate atherosclerosis. Methods Immune infiltration of 69 atheromatous plaques from different arterial beds in GSE100927 were explored by single-sample-gene-set enrichment analysis (presented as ssGSEA scores), ESTIMATE algorithm (presented as immune scores) and CIBERSORT algorithm (presented as relative fractions of 22 types of immune cells) to divide these plaques into ImmuneScoreL cluster (of low immune infiltration) and ImmuneScoreH cluster (of high immune infiltration). Subsequently, comprehensive bioinformatics analyses including differentially-expressed-genes (DEGs) analysis, protein–protein interaction networks analysis, hub genes analysis, Gene-Ontology-terms and KEGG pathway enrichment analysis, gene set enrichment analysis, analysis of expression profiles of immune-related genes, correlation analysis between DEGs and hub genes and immune cells were conducted. GSE28829 was analysed to cross-validate the results in GSE100927. Results Immune-related pathways, including interferon-related pathways and PD-1 signalling, were highly enriched in the ImmuneScoreH cluster. HLA-related (except for HLA-DRB6) and immune checkpoint genes (IDO1, PDCD-1, CD274(PD-L1), CD47), RORC, IFNGR1, STAT1 and JAK2 were upregulated in the ImmuneScoreH cluster, whereas FTO, CRY1, RORB, and PER1 were downregulated. Atheromatous plaques in the ImmuneScoreH cluster had higher proportions of M0 macrophages and gamma delta T cells but lower proportions of plasma cells and monocytes (p < 0.05). CAPG, CECR1, IL18, IGSF6, FBP1, HLA-DPA1 and MMP7 were commonly related to these immune cells. In addition, the advanced-stage carotid plaques in GSE28829 exhibited higher immune infiltration than early-stage carotid plaques. Conclusions Atheromatous plaques with higher immune scores were likely at a more clinically advanced stage. The progression of atherosclerosis might be related to CAPG, IGSF6, IL18, CECR1, FBP1, MMP7, FTO, CRY1, RORB, RORC, PER1, HLA-DPA1 and immune-related pathways (IFN-γ pathway and PD-1 signalling pathway). These genes and pathways might play important roles in regulating immune cells such as M0 macrophages, gamma delta T cells, plasma cells and monocytes and might serve as potential therapeutic targets for atherosclerosis.

Interferon Regulatory Factor 4 (IRF4) is a Prognostic Marker and Related to Immune Infiltration in Breast and Colorectal Cancers

2020 ◽  
Author(s):  
Qingyan Huang ◽  
Zhikang Yu ◽  
Yuhong Gan ◽  
Heming Wu ◽  
Zhixiong Zhong
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Enrichment Analysis ◽  
Interferon Regulatory Factor ◽  
Colorectal Cancers ◽  
Regulatory Factor ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Prognostic Outcome ◽  
Interferon Regulatory Factor 4

Abstract Background: Interferon regulatory factor 4 (IRF4) is a transcription factor that involves in immune cells differentiation. However, it is not clear the relationship between IRF4 and tumor prognosis and immune infiltration.Methods: IRF4 expression levels in different cancers and corresponding normal tissues were analyzed by Oncomine database and Tumor Immune Estimation Resource (TIMER). The prognosis value of IRF4 was assessed by PrognoScan and Kaplan-Meier plotter. The correlation between IRF4 and tumor-infiltrating immune cells and immune cells markers was performed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). In addition, we explored the genes regulated by IRF4 in Gene Transcription Regulation Database (GTRD) and then put the above genes in Enrich online tool for Gene Ontology (GO) and pathway enrichment analysis.Results: Decreased expression levels of IRF4 were observed in breast and colorectal cancers. Survival analysis shown that high level of IRF4 was associated with better prognostic outcome in breast and colorectal cancer patients. IRF4 expression was positively correlated with infiltrating levels of B cells, CD8+ T cells, T cells (general), dendritic cells (DCs), Th1, T cell exhaustion and monocytes, and immune cells markers. Beside, functional enrichment analysis of the potential genes regulated by IRF4 indicated that IRF4 may be involved in many important biological processes including immune regulation by regulating various genes.Conclusions: High expression of IRF4 shown better prognostic outcome for breast and colorectal cancers. IRF4 was associated with immune infiltration in breast and colorectal cancers. Therefore, IRF4 maybe serve as a potential prognostic biomarker in breast and colorectal cancers with immune infiltration.

scholarly journals CLDN6 and CLDN10 are Associated with Immune Infiltration of Ovarian Cancer: A Study of Claudin Family

2020 ◽  
Author(s):  
Peipei Gao ◽  
Ting Peng ◽  
Canhui Cao ◽  
Shitong Lin ◽  
Ping Wu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Gene Markers ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
The Relationship

Abstract Background: Claudin family is a group of membrane proteins related to tight junction. There are many studies about them in cancer, but few studies pay attention to the relationship between them and the tumor microenvironment. In our research, we mainly focused on the genes related to the prognosis of ovarian cancer, and explored the relationship between them and the tumor microenvironment of ovarian cancer.Methods: The cBioProtal provided the genetic variation pattern of claudin gene family in ovarian cancer. The ONCOMINE database and Gene Expression Profiling Interactive Analysis (GEPIA) were used to exploring the mRNA expression of claudins in cancers. The prognostic potential of these genes was examined via Kaplan-Meier plotter. Immunologic signatures were enriched by gene set enrichment analysis (GSEA). The correlations between claudins and the tumor microenvironment of ovarian cancer were investigated via Tumor Immune Estimation Resource (TIMER).Results: In our research, claudin genes were altered in 363 (62%) of queried patients/samples. Abnormal expression levels of claudins were observed in various cancers. Among them, we found that CLDN3, CLDN4, CLDN6, CLDN10, CLDN15 and CLDN16 were significantly correlated with overall survival of patients with ovarian cancer. GSEA revealed that CLDN6 and CLDN10 were significantly enriched in immunologic signatures about B cell, CD4 T cell and CD8 T cell. What makes more sense is that CLDN6 and CLDN10 were found related to the tumor microenvironment. CLDN6 expression was negatively correlated with immune infiltration level in ovarian cancer, and CLDN10 expression was positively correlated with immune infiltration level in ovarian cancer. Further study revealed the CLDN6 expression level was negatively correlated with gene markers of various immune cells in ovarian cancer. And, the expression of CLDN10 was positive correlated with gene markers of immune cells in ovarian cancer.Conclusions: CLDN6 and CLDN10 were prognostic biomarkers, and correlated with immune infiltration in ovarian cancer. Our results revealed new roles for CLDN6 and CLDN10, and they were potential therapeutic targets in the treatment of ovarian cancer.

scholarly journals SCG2 is a Prognostic Biomarker Associated With Immune Infiltration and Macrophage Polarization in Colorectal Cancer

2022 ◽  
Vol 9 ◽  
Author(s):  
Hao Wang ◽  
Jinwen Yin ◽  
Yuntian Hong ◽  
Anli Ren ◽  
Haizhou Wang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Immune Cells ◽  
Macrophage Polarization ◽  
Clinical Stage ◽  
Enrichment Analysis ◽  
Functional Enrichment ◽  
Secretory Proteins ◽  
Advanced Clinical Stage ◽  
Multiple Tumor ◽  
Immune Infiltration

Colorectal cancer (CRC) is the second most lethal malignancy around the world. Limited efficacy of immunotherapy creates an urgent need for development of novel treatment targets. Secretogranin II (SCG2) is a member of the chromogranin family of acidic secretory proteins, has a role in tumor microenvironment (TME) of lung adenocarcinoma and bladder cancer. Besides, SCG2 is a stroma-related gene in CRC, its potential function in regulating tumor immune infiltration of CRC needs to be fully elucidated. In this study, we used western blot, real-time PCR, immunofluorescence and public databases to evaluate SCG2 expression levels and distribution. Survival analysis and functional enrichment analysis were performed. We examined TME and tumor infiltrating immune cells using ESTIMATE and CIBERSORT algorithm. The results showed that SCG2 expression was significantly decreased in CRC tumor tissues, and differentially distributed between tumor and adjacent normal tissues. SCG2 was an independent prognostic predictor in CRC. High expression of SCG2 correlated with poor survival and advanced clinical stage in CRC patients. SCG2 might regulate multiple tumor- and immune-related pathways in CRC, influence tumor immunity by regulating infiltration of immune cells and macrophage polarization in CRC.

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