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

2019 ◽  
Author(s):  
Zhaonian Hao ◽  
Dongsheng Guo

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.

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhaonian Hao ◽  
Dongsheng Guo

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.


2020 ◽  
Author(s):  
Siyuan Jiang ◽  
Lizhe Zhu ◽  
Chao Jiang ◽  
Shibo Yu ◽  
Bin Wang ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shuai Liu ◽  
Xing Liu ◽  
Chuanbao Zhang ◽  
Wei Shan ◽  
Xiaoguang Qiu

Background: Hypoxia-inducible factor 1α (HIF1A), the principal regulator of hypoxia, is involved in the suppression of antitumor immunity. We aimed to describe the T-cell exhaustion status of gliomas under different levels of HIF1A expression.Methods: In this study, 692 patients, whose data were collected from the Chinese Glioma Genome Atlas (CGGA) database, and 669 patients, whose data were collected from The Cancer Genome Atlas database, were enrolled. We further screened the data of a cohort of paired primary and recurrent patients from the CGGA dataset (n = 50). The abundance of immune cells was calculated using the transcriptome data. The association between HIF1A and T-cell exhaustion-related genes and immune cells was investigated.Results: According to the median value of HIF1A expression, gliomas were classified into low-HIF1A-expression and high-HIF1A-expression groups. The expression levels of PDL1 (CD274), FOXO1, and PRDM1 in the high-HIF1A-expression group were significantly higher in both glioblastoma (GBM) and lower-grade glioma. The abundance of exhausted T cells and B cells was significantly higher in the high-HIF1A-expression group, while that of macrophage, monocyte, and natural killer cell was significantly higher in the low-HIF1A-expression group in both GBM and lower-grade glioma. After tumor recurrence, the expression of HIF1A significantly increased, and the correlation between HIF1A expression levels and exhausted T cells and induced regulatory T cells became stronger.Conclusion: In diffuse gliomas, the levels of T-cell exhaustion-associated genes and the abundance of immune cells were elevated under high HIF1A expression. Reversing hypoxia may improve the efficacy of immunotherapy.


2020 ◽  
Vol 2020 ◽  
pp. 1-26
Author(s):  
Qiang Ju ◽  
Xinmei Li ◽  
Heng Zhang ◽  
Songxia Yan ◽  
Ying Li ◽  
...  

Nuclear factor, erythroid 2 like 2 (NFE2L2, NRF2) is a transcription factor that regulates various antioxidant enzymes. It plays a vital physiological role in regulating oxidative stress and inflammatory response. However, the roles of NFE2L2 in human cancers are still unclear. Our study is aimed at analyzing the prognostic value of NFE2L2 in pan-cancer and at revealing the relationship between NFE2L2 expression and tumor immunity. The present study revealed that NFE2L2 was abnormally expressed and significantly correlated with mismatch repair (MMR) gene mutation levels and DNA methyltransferase expression in human pan-cancer. In particular, pan-cancer survival analysis indicated that NFE2L2 expression was associated with adverse outcomes—overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI)—in adrenocortical carcinoma (ACC), brain lower grade glioma (LGG), and pancreatic adenocarcinoma (PAAD) patients. A positive relationship was also found between NFE2L2 expression and immune infiltration, including B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells, especially in breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), kidney renal clear cell carcinoma (KIRC), LGG, liver hepatocellular carcinoma (LIHC), and prostate adenocarcinoma (PRAD). Additionally, NFE2L2 expression was positively correlated with the immune score and the expression of immune checkpoint markers in LGG. In conclusion, these results indicate that transcription factor NFE2L2 is a potential prognostic biomarker and is correlated with immune infiltration in LGG.


2019 ◽  
Author(s):  
Xi Zhou ◽  
Zhengjiang Ling ◽  
Bing Yang

AbstractObjectiveThe prognostic effect of tumor-infiltrating immune cells (TIICs) on endometrial cancer (EMC) has not been extensively investigated. In the present study, we systematically analyzed the role of TIICs in EMC development.MethodsPatient data were downloaded from The Cancer Genome Atlas (TCGA). We comprehensively analyzed TIIC population in EMC tissue and their role in EMC progression and prognosis by using a deconvolution algorithm (CIBERSORT) and clinically annotated expression profiles.ResultsThe proportions of gamma delta T cells, resting NK cells, M1 macrophages, and resting mast cells were significantly different in normal endometrium and EMC tissue. The proportion of CD8+ T cells, resting memory CD4 T cells, and M0 macrophages was reversed middle correlated. The proportion of resting dendritic cells, resting memory CD4 T cells, and T regulatory cells (Tregs) decreased in accordance with the cancer cell differentiation grade (G); the lower proportion of activated dendritic cells and gamma delta T cells and higher proportion of Tregs predicted longer EMC survival time and vice versa. The low proportion of gamma delta T cells indicated better response to therapy.ConclusionCollectively, our data suggested subtle differences in the cellular composition of TIICs in EMC, and these differences were likely to be important determinants of both prognosis and therapy of EMC.


2009 ◽  
Vol 23 (6) ◽  
pp. 760-766 ◽  
Author(s):  
Pu Feng ◽  
Karen K. Yee ◽  
Nancy E. Rawson ◽  
Lauren M. Feldman ◽  
Roy S. Feldman ◽  
...  

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jake W. Rhodes ◽  
Rachel A. Botting ◽  
Kirstie M. Bertram ◽  
Erica E. Vine ◽  
Hafsa Rana ◽  
...  

AbstractTissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. As such they deliver HIV to its primary target cells; CD4 T cells. Most MNP HIV transmission studies have focused on epithelial MNPs. However, as mucosal trauma and inflammation are now known to be strongly associated with HIV transmission, here we examine the role of sub-epithelial MNPs which are present in a diverse array of subsets. We show that HIV can penetrate the epithelial surface to interact with sub-epithelial resident MNPs in anogenital explants and define the full array of subsets that are present in the human anogenital and colorectal tissues that HIV may encounter during sexual transmission. In doing so we identify two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 (cDC2).


2011 ◽  
Vol 188 (3) ◽  
pp. 1168-1177 ◽  
Author(s):  
Xiongfei Xu ◽  
Hai Yi ◽  
Zhenhong Guo ◽  
Cheng Qian ◽  
Sheng Xia ◽  
...  

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