Prognostic and immune roles of synaptotagmin-4 in gastric cancer and brain lower-grade glioma

2020 ◽  
Author(s):  
Siyuan Jiang ◽  
Lizhe Zhu ◽  
Chao Jiang ◽  
Shibo Yu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Cells ◽  
Treg Cells ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Lower Grade Glioma ◽  
Close Relationship ◽  
Human Protein Atlas ◽  
The Relationship

Abstract Background Synaptotagmins (SYTs) are a family of proteins whose primary function is serving as a calcium sensor in vesicle transport and exocytosis, playing an important role in the function of immune cells. There is also a close relationship between immune cells and tumours. SYT4 is one molecule involved in this relationship, but the relationship between SYT4 and cancer remains unclear. Therefore, we hypothesize that SYT4 can affect the prognosis of cancer, and may be related to immune cells. Methods The following databases were used to study the immunological and prognostic role of SYT4 in cancers: Oncomine, Kaplan-Meier plotter, The Human Protein Atlas, CCLE, GEPIA2, TIMER, and CGGA. Results SYT4 expressions were lower in many cancers than in normal tissues. Specifically in gastric cancer and lower-grade gliomas, SYT4 played a protective and harmful role, respectively. Moreover, a difference between SYT4 expression and the levels of immune infiltration existed in stomach adenocarcinoma (STAD) and brain lower-grade glioma (LGG). In addition, we found that the relationship between markers of monocytes, M1 and M2 macrophages, tumour-associated macrophages (TAMs), Treg cells, B lymphocytes, dendritic cells (DCs) and SYT4 expression was opposite in STAD and LGG. Conclusions The effect of SYT4 on the prognosis of patients with STAD and LGG was opposite. And SYT4 has different effects on immune infiltration in these two tumours. Therefore, SYT4 might be a potential prognostic and tumour immune-related biomarker in STAD and LGG.

scholarly journals Prognosis and immune function of Synaptotagmin-4 in gastric cancer and brain low-grade glioma

2020 ◽  
Author(s):  
Siyuan Jiang ◽  
Lizhe Zhu ◽  
Chao Jiang ◽  
Shibo Yu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Immune Function ◽  
Treg Cells ◽  
Low Grade Glioma ◽  
Low Grade ◽  
Lower Grade ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Kaplan Meier

Abstract Background Synaptotagmins (SYTs) are a family of proteins whose primary feature is the calcium sensor in vesicle transport and exocytosis. SYT4 is one of them, but the relationship between SYT4 and cancer remains unclear. We aim to explore the prognosis and immune function of SYT4 in gastric cancer and low-grade glioma. Methods These databases were used to study the immunological and prognostic role of SYT4 in cancers, including the Oncomine database, Kaplan-Meier plotter, GEPIA2, TIMER, and CGGA. Results The study suggested that the expression levels of SYT4 were lower in both gastric cancer and glioma, compared to the normal tissues. And SYT4 played a protective and harmful role in low-grade gliomas and gastric cancer, respectively. Moreover, we found that a difference between SYT4 expression and the levels of immune infiltration in stomach adenocarcinoma (STAD) and brain lower-grade glioma (LGG). Besides, after exploring the association between the expression levels of SYT4 and markers of immune cells in these two cancers, we found that markers of monocytes, M1/ M2, tumor-associated macrophages (TAMs), Treg cells and SYT4 expressions had an opposite correlation in STAD and LGG. Conclusions SYT4 had an effect on the prognosis of gastric cancer and glioma patients and was related to immune infiltration by regulating TAMs and Treg cells. SYT4 can be used as a prognostic biomarker for STAD and LGG.

scholarly journals Immune Cell Landscape in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yang Yang ◽  
Wei He ◽  
Zi-rui Wang ◽  
Yu-jiao Wang ◽  
Lan-lan Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
B Cells ◽  
Immune Cells ◽  
Immune Cell ◽  
Univariate Analysis ◽  
Molecular Therapy ◽  
Expression Level ◽  
Regulatory Factors ◽  
Normal Tissues ◽  
The Relationship

Background. The tumor-infiltrating immune cells are closely associated with the prognosis of gastric cancer (GC). This article is aimed at determining the composition change of immune cells and immune regulatory factors in GC and normal tissues, depicting their prognosis value in GC, and revealing the relationship between them and GC clinical parameters. Methods. We used CIBERSORT to calculate the proportion of 22 immune cells in the GC or normal tissues; a t -test was applied to assess the expression difference of immune cells and immune regulatory factors in normal and GC tissues. The relationship of the immune cells, immune regulatory factors, and GC patients’ clinical characteristics was assessed by univariate analysis. Results. In this study, we found that the proportion of macrophages increased, while plasma cells and monocytes decreased in GC tissues. In these immune fractions, Tregs and naïve B cells were found to be correlated with GC patients’ prognosis. Interestingly, the expression of immune regulatory factors was ambiguous with their classical function in GC tissues. For example, TIM-3, FOXP3, and CMTM6 were overexpressed, while CD27 and PD-1 were underexpressed in GC tissues. We also found that IDO1, PD-1, TIGIT, and TIM-3 were highly expressed in high-grade GC tissues, the HERC2 expression level was related to patients’ gender, and the TIGIT expression level was sensitive to targeted therapy. Furthermore, our results suggested that the infiltration of Tregs and naive B cells was strongly correlated with the T stage, radiation therapy, targeted molecular therapy, and the expression levels of TIM-3 and FOXP3 in GC. Conclusion. The expression pattern of tumor-infiltrating immune cells and immune regulatory factors was systematically depicted in the GC tumor microenvironment, indicating that individualized treatment based on the tumor-infiltrating immune cells and immune regulatory factors may be beneficial to GC patients.

scholarly journals EGFR mutation: a prognostic factor associated with immune infiltration in lower-grade glioma.

2019 ◽  
Author(s):  
Zhaonian Hao ◽  
Dongsheng Guo
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Cells ◽  
Cd4 T Cells ◽  
Egfr Mutation ◽  
Biological Effects ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Lower Grade Glioma ◽  
Egfr Mutant

Abstract Glioma is one of the most common type of primary central nervous system (CNS) tumors. EGFR mutation, a common alteration occurs in various tumors, is not brought to the forefront in understanding and treating glioma at present. In the present study, we demonstrated an immune infiltration related pattern of EGFR mutation in lower-grade glioma. In silico analyses were performed to investigate EGFR mutation and its biological effects and clinical values. GO and GSEA process were used as enrichment analysis. Infiltration levels of specific types of immune cells were estimated at TIMER database. Clinical data of patients were obtained from TCGA and were employed for survival analyses. Results revealed that EGFR mutation leads to an up-regulation of immune response related pathways and dismal prognosis in lower-grade glioma. Infiltration of CD4+ T cells, neutrophils, macrophages, and dendritic cells were significantly increased in EGFR-mutant cases. Infiltration of specific types of immune cells were correlated with shorter survival time. PD-L1 was elevated in EGFR-mutant cases and correlated with infiltration level of CD4+ T cells, neutrophils and dendritic cells. In conclusion, EGFR mutation indicates increasing infiltration of specific types of immune cells and poor prognosis in lower-grade glioma. Alteration of immune microenvironment since the EGFR mutation might influence the survival of glioma. We also provided a novel evidence and indicator of PD-1 inhibitor application in glioma.

scholarly journals EGFR mutation: novel prognostic factor associated with immune infiltration in lower-grade glioma; an exploratory study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhaonian Hao ◽  
Dongsheng Guo
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Cells ◽  
Cd4 T Cells ◽  
Egfr Mutation ◽  
Biological Effects ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Lower Grade Glioma ◽  
Egfr Mutant

Abstract Background Glioma is one of the most common type of primary central nervous system tumors. EGFR mutation, a common alteration occurs in various tumors, is not brought to the forefront in understanding and treating glioma at present. Methods In the present study, we demonstrated an immune infiltration related pattern of EGFR mutation in lower-grade glioma. In silico analyses were performed to investigate EGFR mutation and its biological effects and clinical values. GO and GSEA process were used as enrichment analysis. Infiltration levels of specific types of immune cells were estimated at TIMER database. Clinical data of patients were obtained from TCGA and were employed for survival analyses. Results Here we revealed that EGFR mutation leads to an up-regulation of immune response related pathways and dismal prognosis in lower-grade glioma. Infiltration of CD4+ T cells, neutrophils, macrophages, and dendritic cells were significantly increased in EGFR-mutant cases. Infiltration of specific types of immune cells were correlated with shorter survival time. PD-L1 was elevated in EGFR-mutant cases and correlated with infiltration level of CD4+ T cells, neutrophils and dendritic cells. Conclusion EGFR mutation indicates increasing infiltration of specific types of immune cells and poor prognosis in lower-grade glioma. Alteration of immune microenvironment since the EGFR mutation might influence the survival of glioma. We also provided a novel evidence and indicator of PD-1 inhibitor application in glioma.

scholarly journals Prognostic Value and Immunological Role of MORF4-Related Gene-Binding Protein in Human Cancers

2021 ◽  
Vol 9 ◽  
Author(s):  
Dongqi Chai ◽  
Lilong Zhang ◽  
Yongjun Guan ◽  
Jingping Yuan ◽  
Man Li ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Binding Protein ◽  
Macrophage Infiltration ◽  
Lower Grade ◽  
Related Gene ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Human Cancers ◽  
The Relationship

MORF4-related gene-binding protein (MRGBP) is the subunit of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. Much of the research indicated an oncogenic role of MRGBP in the development of cancers. However, it is still unknown the role MRGBP plays in human cancers, which deserves further exploration. In this research, the expression profile, prognostic value of MRGBP, and the relationship between MRGBP and immune infiltration were explored in 33 types of cancer. The differences in MRGBP expression in tumor and normal tissues were explored using data from The Cancer Genome Atlas, Gene Expression Omnibus and ONCOMINE. Analysis of the association between MRGBP and prognosis using Kaplan-Meier survival curve and COX analysis. The data of Tumor mutational burden (TMB), microsatellite instability (MSI) from TCGA. The relationship Between MRGBP expression and immunity was analyzed using the ESTIMATE algorithm and CIBERSORT. Furthermore, we explored MRGBP expression and the relationship between MRGBP expression and macrophage infiltration using immunohistochemical analysis in lower grade glioma (LGG). Our results revealed that MRGBP was highly expressed in most cancer tissues compared with normal tissues. Tumors with increased MRGBP expression had a high clinicopathologic stage and poor prognosis. The expression of MRGBP was closely related to the TMB, MSI. We also found a significant negative correlation between MRGBP expression and stromal scores and immune scores in various types of cancer. Furthermore, MRGBP expression was associated with a variety of immune cells including B cells, NK cells, T cells, and macrophages. LGG and LIHC was selected as representative cancer types for further study, the results of immunohistochemistry indicated that the protein levels of MRGBP were significantly elevated in tumor tissues. Moreover, our LIHC data analysis showed that patients with high MRGBP expression were associated with short survival rates and MRGBP was a risk factor to determine OS. Immunohistochemistry also confirmed that M0 macrophage infiltration in the MRGBP-high group significantly increased. In conclusion, these results reveal that MRGBP can serve as a potential prognostic biomarker and it plays an important role in tumor immune infiltration in various tumors, especially in LGG and LIHC.

scholarly journals Novel Biomarker Genes for Prognosis of Survival and Treatment of Glioma

2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaopeng Zhu ◽  
Sian Pan ◽  
Rui Li ◽  
Zebo Chen ◽  
Xingyun Xie ◽  
...  
Keyword(s):  
Immune Cell ◽  
Large Degree ◽  
Lower Grade ◽  
Central Nervous System Tumor ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Lower Grade Glioma ◽  
Tumor Mutational Burden ◽  
System Tumor ◽  
The Relationship

Glioblastoma multiforme (GBM) is the most aggressive malignant primary central nervous system tumor. Although surgery, radiotherapy, and chemotherapy treatments are available, the 5-year survival rate of GBM is only 5.8%. Therefore, it is imperative to find novel biomarker for the prognosis and treatment of GBM. In this study, a total of 141 differentially expressed genes (DEGs) in GBM were identified by analyzing the GSE12657, GSE90886, and GSE90598 datasets. After reducing the data dimensionality, Kaplan-Meier survival analysis indicated that expression of PTPRN and RIM-BP2 were downregulated in GBM tissues when compared with that of normal tissues and that the expression of these genes was a good prognostic biomarker for GBM (p<0.05). Then, the GSE46531 dataset and the Genomics of Drug Sensitivity in Cancer (GDSC) database were used to examine the relationship between sensitivity radiotherapy (RT) and chemotherapy for GBM and expression of PTPRN and RIM-BP2. The expression of PTPRN was significantly high in RT-resistant patients (p<0.05) but it was not related to temozolomide (TMZ) resistance. The expression level of RIM-BP2 was not associated with RT or TMZ treatment. Among the chemotherapeutic drugs, cisplatin and erlotinib had a significantly good treatment effect for glioma with expression of PTPRN or RIM-BP2 and in lower-grade glioma (LGG) with IDH mutation. (p < 0.05). The tumor mutational burden (TMB) score in the low PTPRN expression group was significantly higher than that in the high PTPRN expression group (p=0.013), with a large degree of tumor immune cell infiltration. In conclusion, these findings contributed to the discovery process of potential biomarkers and therapeutic targets for glioma patients.

scholarly journals Genome-Wide Transcriptomic Analysis of Non-Tumorigenic Tissues Reveals Aging-Related Prognostic Markers and Drug Targets in Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3045
Author(s):  
Euiyoung Oh ◽  
Jun-Hyeong Kim ◽  
JungIn Um ◽  
Da-Woon Jung ◽  
Darren R. Williams ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cancer Patient ◽  
Immune Cells ◽  
Renal Cell ◽  
Prognostic Markers ◽  
Patient Survival ◽  
Survival Outcome ◽  
Normal Tissues ◽  
Genome Wide ◽  
The Relationship

The relationship between expression of aging-related genes in normal tissues and cancer patient survival has not been assessed. We developed a genome-wide transcriptomic analysis approach for normal tissues adjacent to the tumor to identify aging-related transcripts associated with survival outcome, and applied it to 12 cancer types. As a result, five aging-related genes (DUSP22, MAPK14, MAPKAPK3, STAT1, and VCP) in normal tissues were found to be significantly associated with a worse survival outcome in patients with renal cell carcinoma (RCC). This computational approach was investigated using nontumorigenic immune cells purified from young and aged mice. Aged immune cells showed upregulated expression of all five aging-related genes and promoted RCC invasion compared to young immune cells. Further studies revealed DUSP22 as a regulator and druggable target of metastasis. DUSP22 gene knockdown reduced RCC invasion and the small molecule inhibitor BML-260 prevented RCC dissemination in a tumor/immune cell xenograft model. Overall, these results demonstrate that deciphering the relationship between aging-related gene expression in normal tissues and cancer patient survival can provide new prognostic markers, regulators of tumorigenesis and novel targets for drug development.

scholarly journals CXC Chemokines as Therapeutic Targets and Prognostic Biomarkers in Skin Cutaneous Melanoma Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Xuezhi Zhou ◽  
Manjuan Peng ◽  
Ye He ◽  
Jingjie Peng ◽  
Xuan Zhang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Cutaneous Melanoma ◽  
Immune Cell ◽  
Gene Activation ◽  
Skin Tumor ◽  
Pathological Stage ◽  
Normal Tissues ◽  
The World ◽  
Cxc Chemokine ◽  
The Relationship

BackgroundSkin Cutaneous Melanoma (SKCM) is a tumor of the epidermal melanocytes induced by gene activation or mutation. It is the result of the interaction between genetic, constitutional, and environmental factors. SKCM is highly aggressive and is the most threatening skin tumor. The incidence of the disease is increasing year by year, and it is the main cause of death in skin tumors around the world. CXC chemokines in the tumor microenvironment can regulate the transport of immune cells and the activity of tumor cells, thus playing an anti-tumor immunological role and affecting the prognosis of patients. However, the expression level of CXC chemokine in SKCM and its effect on prognosis are still unclear.MethodOncomine, UALCAN, GEPIA, STRING, GeneMANIA, cBioPortal, TIMER, TRRUST, DAVID 6.8, and Metascape were applied in our research.ResultThe transcription of CXCL1, CXCL5, CXCL8, CXCL9, CXCL10, and CXCL13 in SKCM tissues were significantly higher than those in normal tissues. The pathological stage of SKCM patients is closely related to the expression of CXCL4, CXCL9, CXCL10, CXCL11, CXCL12, and CXCL13. The prognosis of SKCM patients with low transcription levels of CXCL4, CXCL9, CXCL10, CXCL11, and CXCL13 is better. The differential expression of CXC chemokines is mainly associated with inflammatory response, immune response, and cytokine mediated signaling pathways. Our data indicate that the key transcription factors of CXC chemokines are RELA, NF-κB1 and SP1. The targets of CXC chemokines are mainly LCK, LYN, SYK, MAPK2, MAPK12, and ART. The relationship between CXC chemokine expression and immune cell infiltration in SKCM was closed.ConclusionsOur research provides a basis for screening SKCM biomarkers, predicting prognosis, and choosing immunotherapy.

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.

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