scholarly journals FCGR1A Serves as a Novel Biomarker and Correlates With Immune Infiltration in Four Cancer Types

2020 ◽  
Vol 7 ◽  
Author(s):  
Ji-li Xu ◽  
Yong Guo

BackgroundFCGR1A encodes a protein that plays an important role in the immune response. The prognostic impact and immune infiltration of FCGR1A in heterogeneous cancers remain unclear.MethodsDifferential expression of FCGR1A between tumor and normal tissues and the discrepancies in overall survival (OS) among diverse cancer types were performed by Gene Expression Profiling Interactive Analysis. The correlation between FCGR1A and immune cells or gene marker sets of immune infiltrates was analyzed via Tumor Immune Estimation Resource (TIMER). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-to-protein interaction (PPI) network were used to explore the function and related genes of FCGR1A. The relationships among these genes were further analyzed by TIMER.ResultsFCGR1A is highly expressed in various cancer types. FCGR1A was significantly correlated with the OS of cervical and endocervical cancer (CESC), cholangiocarcinoma (CHOL), kidney renal clear cell carcinoma (KIRC), and skin cutaneous melanoma (SKCM) (P < 0.05). High expression of FCGR1A meant a better prognosis besides KIRC. FCGR1A showed significant differences at different stages of KIRC and SKCM (P < 0.05). Furthermore, FCGR1A was notably associated with infiltrating levels of CD4+ T cells, CD8+ T cells, B cells, macrophages, neutrophils, and dendritic cells in the four cancers (P < 0.05). FCGR1A also showed close relevance with different immune gene markers. The copy number variation of FCGR1A significantly influenced the abundance of immune infiltration in KIRC and SKCM. GO, KEGG analysis, and PPI network analysis revealed that FCGR1A is involved in many pathophysiological processes and was most related to FCGR3A. And this gene indicated highly significant positive correlations with FCGR1A in four cancers.ConclusionFCGR1A may be a potential prognostic biomarker and related to immune infiltration levels in diverse cancers, especially in CESC, CHOL, KIRC, and SKCM. Besides, FCGR1A may be involved in the activation, regulation, or induction of immune cells and diverse physiological and pathological processes.

2021 ◽  
Author(s):  
Hailing Duan ◽  
Ying Lv ◽  
Pan Liao ◽  
Yiming Wang ◽  
Zhifang Zheng ◽  
...  

Abstract Background: CXCL13 is an important chemotactic factor closely related to the biology of cancer cells. The presence work focused on exploring the significance of CXCL13 in prognosis prediction and analyzing the associations of CXCL13 with T cell function and immune infiltration in various cancers, especially ovarian cancer (OV).Purpose: CXCL13 is associated with prognosis, immune infiltration, and T cell failure of ovarian cancer.Methods: The Oncomine, GEPIA2 and HPA databases were utilized for analyzing CXCL13 levels within diverse cancers. The significance of CXCL13 in prognosis prediction was explored through Kaplan-Meier Plotter, TCGAportal, and GEPIA2. Meanwhile, the associations of CXCL13 with clinical stage, gene marker sets, and immune infiltration were examined through TISIDB, GEPIA2, and TIMER databases. Besides, CXCL13 was screened to analyze the biological processes (BPs) and KEGGs enriched by co-expression genes. The miRWalk database was employed for analyzing the gene-miRNA interaction network of CXCL13 within OV.Results: CXCL13 expression decreased in many cancers, which predicted the dismal survival of OV. CXCL13 upregulation was in direct proportion to the increased immune infiltration degrees of many functional T cells (like exhausted T cells) and immune cells. Additionally, some critical genes of exhausted T cells, such as TIM-3, PD-1, LAG3, TIGIT, GZMB, and CXCL13, were closely associated with CXCL13. Moreover, CXCL13 was related to immune response regulatory signaling pathway, leukocyte cell-cell adhesion, cell adhesion molecules (CAMs), and hematopoietic cell lineage. Conclusion: CXCL13 can serve as a biomarker to predict cancer prognosis, particularly OV. CXCL13 upregulation remarkably elevates the immune infiltration degrees of numerous immune cells, like mast cells, CD8+ T cells, natural killer (NK) cells, and dendritic cells (DCs). Furthermore, CXCL13 is suggested to be closely related to exhausted T cells, which may be used as a candidate regulating factor for T cell exhaustion within OV. Detecting CXCL13 levels contributes to prognosis prediction and CXCL13 regulation within exhausted T cells, which provides a new approach to maximizing the anti-OV efficacy of immunotherapy.


Author(s):  
Jili Xu ◽  
Yong Guo

Abstract Background: FCGR1A encodes a protein that plays an important role in the immune response. The prognosis and tumor immune infiltration of FCGR1A in heterogeneous tumors remains unclear.Methods: Differential expression analysis of FCGR1A between tumor and normal tissues and the difference in overall survival (OS) among different cancer types were performed by Gene Expression Profiling Interactive Analysis (GEPIA). The correlation between FCGR1A and cancer immune infiltration or immue gene markers was completed through Tumor Immune Estimation Resource (TIMER) site. Results: FCGR1A exhibited high expression in various cancer types. FCGR1A was significantly correlated with the overall survival (OS) of cervical and endocervical cancer (CESC), cholangiocarcinoma (CHOL), kidney renal clear cell carcinoma (KIRC) and skin cutaneous melanoma (SKCM) (P<.05). High expression of FCGR1A meant a better prognosis except for KIRC. FCGR1A showed significant differences at different stages of KIRC and SKCM (P<.05). Furthermore, FCGR1A was notably associated with immune infiltrating levels of CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell in the four cancers (P<.05). FCGR1A also showed close relevance with different immune gene markers. The copy number variation (CNV) of FCGR1A significantly influenced the abundance of immune infiltration in KIRC and SKCM. Conclusion: FCGR1A may be a potential prognostic biomarker and related to immune infiltration levels in diverse cancers, especially in CESC, CHOL, KIRC, and SKCM. Besides, FCGR1A may be involved in the activation, regulation or induction of immune cells.


2020 ◽  
Author(s):  
Yang Wang ◽  
Qiong Chen

Abstract Background Glycoprotein non-metastatic gene B (GPNMB) can regulate tumor progression by interacting with T cell function. However, the association between GPNMB and tumor-infiltrating immune cells and prognosis of various cancers is poorly understood. Methods We use the Oncomine and TIMER database to investigate GPNMB expression in multiple tumors. The PrognoScan database, Kaplan-Meier plotter are used to analyze tumor prognosis of GPNMB. R packages are used to performed multivariable cox regression analysis. We use TIMER and GEPIA database to explore the association between GPNMB expression and tumor immune infiltration levels, and immune cell markers. GPNMB related transcription factors and transcription-target networks are investigated via TTRUST database and GeneMANIA . Results A high level of GPNMB expression was significantly associated with poor prognosis in stomach adenocarcinoma (STAD). While, a high level of GPNMB expression was significantly associated with favorable prognosis in lung adenocarcinoma (LUAD). Besides, GPNMB expression levels can impact the prognosis in STAD and LUAD patients with lymph node metastasis. Moreover, GPNMB expression level has significant relationships with B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils, and DCs infiltrating levels in STAD and LUAD. Besides, various immune gene markers of STAD and LUAD are significantly related to GPNMB expression. In addition, the GPNMB related transcription factors are MITF and TP53. The transcript-target networks are mainly responsible for signal transduction in response to DNA damage, DNA damage response, signal transduction by p53 class mediator, mitotic G1 DNA damage checkpoint, G1 DNA damage checkpoint. Conclusions These results indicate that GPNMB is significantly associated with prognosis and immune infiltrating levels in various cancers patients, especially in STAD, LUAD patients. Multiple immune gene markers of STAD and LUAD are significantly related to GPNMB expression, especially monocyte, macrophage polarization, and functional T cells gene markers. Our study signifies that GPNMB plays an essential role in prognosis prediction and immune infiltration of STAD and LUAD.


2020 ◽  
Author(s):  
Jia-yi XIE ◽  
Ming Liu ◽  
Yaxin Luo ◽  
Zhen Wang ◽  
Zhenghong Lu ◽  
...  

Abstract PurposeEsophageal cancer (EC) is the sixth leading cause of cancer death worldwide. Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of EC. Identifying diagnostic biomarkers for ESCC is necessary for cancer practice. Increasing evidence illustrates that apolipoprotein C-1 (APOC1) participates in the carcinogenesis. However, the biological function of APOC1 in ESCC remains unclear. Patients and methodsWe investigated the expression level of APOC1 using TIMER2.0 and GEO databases, the prognostic value of APOC1 in ESCC using Kaplan-Meier plotter and TCGA databases. We used LinkedOmics to identify co-expressed genes with APOC1 and perform GO and KEGG pathway analysis. The target networks of kinases, miRNAs and transcription factors were predicted by gene set enrichment analysis (GSEA). The correlations between APOC1 and immune infiltration were calculated using TIMER2.0 and CIBERSORT databases. We further performed the prognostic analysis based on APOC1 expression levels in related immune cells subgroups via Kaplan-Meier plotter database. ResultsAPOC1 was found overexpressed in tumor tissues in multiple ESCC cohorts and high APOC1 expression was related to a dismal prognosis. Multivariate analysis confirmed that APOC1 overexpression was an independent indicator of poor OS. Functional network analysis indicated that APOC1 might regulate the natural killer cell mediated cytotoxicity, phagosome, AMPK and hippo signaling through pathways involving some cancer-related kinases, miRNA and transcription factors. Immune infiltration analysis showed that APOC1 was significantly positively correlated with M0 macrophages cells, M1 macrophages cells and activated NK cells, negatively correlated with regulatory T cells, CD8 T cells, neutrophils and monocytes. High APOC1 expression had a poor prognosis in server immune cells subgroups in ESCC, including decreased CD8+ T cells subgroups. ConclusionThese findings suggest that increased expression of APOC1 is related to poor prognosis and immune infiltration in ESCC. APOC1 holds promise for serving as a valuable diagnostic and prognostic marker in ESCC.


2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wenxing Su ◽  
Yuqian Wei ◽  
Biao Huang ◽  
Jiang Ji

BackgroundPsoriasis is a chronic, prolonged, and recurrent skin inflammatory disease. However, the pathogenesis of psoriasis is not completely clear, thus we aimed to explore potential molecular basis of it.MethodsTwo datasets were downloaded from the Gene Expression Omnibus database. After identifying the differentially expressed genes of psoriasis skin lesion samples and healthy controls, three kinds of analyses, namely functional annotation, protein-protein interaction (PPI) network, and immune infiltration analyses, were performed.ResultsA total of 152 up-regulated genes and 38 down-regulated genes were selected for subsequent analyses. Evaluation of the PPI network identified the most important module containing 13 hub genes. Gene ontology analysis showed that the hub genes have a significant enrichment effect on positive regulation of cell migration, defense response to the other organism and epithelial cell differentiation. KEGG signaling pathway analysis showed that the hub genes were significantly enriched in chemokine signaling, Toll-like receptor signaling pathway, and IL-17 signaling pathway. Compared with the normal control sample, naive B cells, CD8+ T cells, activated memory CD4+ T cells, follicular helper T cells, gamma delta T cells, resting NK cells, monocytes, M0 macrophages, M1 macrophages, activated dendritic cells and neutrophils infiltrated more, while memory B cells, naive CD4+ T cells, regulatory T cells (Tregs), activated NK cells, resting mast cells, and eosinophils infiltrated less.ConclusionTo conclude, the hub genes and pathways identified from psoriasis lesions and normal controls along with the immune infiltration profile may provide new insights into the study of psoriasis.


2020 ◽  
Author(s):  
Qingyan Huang ◽  
Zhikang Yu ◽  
Yuhong Gan ◽  
Heming Wu ◽  
Zhixiong Zhong

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.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Xiaohong Liu ◽  
Qian Xu ◽  
Zijing Li ◽  
Bin Xiong

AbstractAquaporin 9 (AQP9), as an aquaglyceroporin, is expressed in many immune cells and plays important role in tumor initiation and progression. However, the relationship between AQP9 and tumor-infiltrating cells, and its prognostic value in cancers still require comprehensive understanding. Herein, we aimed to elucidate the correlations of AQP9 with prognosis and immune infiltration levels in diverse cancers. We detected the expression and survival data of AQP9 through Oncomine, TIMER, Kaplan–Meier Plotter and PrognoScan databases. The correlations between AQP9 and immune infiltrates were analyzed in TIMER database. Our results found that high AQP9 expression was significantly correlated with worse prognosis in breast, colon and lung cancers, while predicted better prognosis in gastric cancer. Moreover, AQP9 had significant association with various immune infiltrating cells including CD8+ and CD4+ T cells, neutrophils, macrophages and dendritic cells (DCs), and diverse immune gene markers in BRCA, COAD, LUAD, LUSC and STAD. AQP9 was also significantly correlated with the regulation of tumor associated macrophages (TAM). These results indicate that AQP9 can play as a significant biomarker to determine the prognosis and the immune infiltrating levels in different cancers. It might also contribute to the development of the immunotherapy in breast, colon, lung and gastric cancers.


2020 ◽  
Author(s):  
Lin Wang ◽  
Qian Wei ◽  
Ming Zhang ◽  
Lianze Chen ◽  
Zinan Li ◽  
...  

Abstract Background Esophageal cancer (ESCA) is one of the deadliest solid malignancies with worse survival in the world. The poor prognosis of ESCA is not only related to malignant cells, but also affected by the microenvironment. We aimed to establish prognostic signature consisting of immune genes to predict the survival outcome of patients and estimate the prognosis value of infiltrating immune cells in tumor microenvironment (TME). Methods Based on integrated analysis of gene expression profiling and immune gene database, differentially immune-related genes were filtered out. Then, stepwise Cox regression analysis was applied to identify survival related immune genes and construct prognosis signature. Functional enrichment analysis was performed to explore biology function. Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves were performed to validate the predictive effect of predictive signature. We also verified the clinical value of prognostic signature under the influence of different clinical parameters. For deeper analysis, we evaluated the correlation between prognosis signature and infiltrating immune cells by Tumor Immune Estimation Resource (TIMER) and CIBERSORT. Results Finally, we identified 303 differentially immune genes as candidate and constructed immune prognosis signature composed of six immune genes. Furthermore, we observed that the prognosis signature was enriched in cytokine-mediated signaling pathway, lymphocyte activation, immune effector process, cancer pathway, NF-kappa B signaling pathway. K-M survival curves showed that the prognosis signature indeed have good predictive ability in entire ESCA set ( P =0.003), validation set 1 ( P =0.008) and validation set 2 ( P =0.036). The area under the curve (AUC) of ROC curves validated the predictive accuracy of immune signature in three cohorts (AUC=0.757, 0.800 and 0.701), respectively. In addition, we identified the prognosis value of infiltrating-immune cells including activated memory CD4 T cells, T cells follicular helper cells and monocytes and provided a landscape of TME. Conclusions The results indicated that immune prognosis signature can be a novel biomarker to predict survival outcome, which can provide new targets for immunotherapy and individualized therapies in ESCA and open up a new prospect for improving the prognosis of ESCA patients in the era of immunotherapy.


2020 ◽  
Author(s):  
Peipei Gao ◽  
Ting Peng ◽  
Canhui Cao ◽  
Shitong Lin ◽  
Ping Wu ◽  
...  

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.


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