scholarly journals CENPF Upregulation is Associated with Immunosuppressive Status and Predicts Poor Clinical Outcomes in Lung Adenocarcinoma Validated by Qrt- PCR

2021 ◽  
Author(s):  
zhiyun xu ◽  
Shi Wang ◽  
Zhijian Ren ◽  
Xiang Gao ◽  
Lin Xu ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Comprehensive Analysis ◽  
Clinical Samples ◽  
R Software ◽  
Qrt Pcr ◽  
Prediction Of Prognosis ◽  
The Relationship

Abstract Background: CENPF was differentially expressed in various cancers. However, the relationship between CENPF and immune infiltrates in lung adenocarcinoma was previously unknown.Methods: We implemented a comprehensive analysis of expression of CENPF in the GEO and TCGA databases. CENPF was evaluated for its prognostic value combining clinical samples from the GEPIA2 and TCGA databases. The Metascape together with WebGestalt databases were used for enrichment analysis of genesets that were most postively associated with CENPF. We retrieved the score for immune cell infiltration in TCGA data and examined the correlation between CENPF expression and the infiltration of immune cell by R software.Results: The outcomes exhibited that up-regulated CENPF mRNA expression was evidently related to poor PFS, DSS and OS in patients with lung adenocarcinoma. Moreover, high expression of CENPF was markedly related to genes associated with immune checkpoint. Further analysis showed that T cell CD4+ Th2 infiltration increased in lung adenocarcinoma samples with high CENPF expression.Conclusions: Our study indicated that CENPF led to T cell CD4+ Th2 infiltration through oncogenic activity and may be employed as a biomarker for the prediction of prognosis in lung adenocarcinoma.

scholarly journals Comprehensive Analysis of Immune-Related Metabolic Genes in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Fangfang Li ◽  
Chun Huang ◽  
Llingxiao Qiu ◽  
Ping Li ◽  
Guojun Zhang
Keyword(s):  
Lung Cancer ◽  
Regression Analysis ◽  
Lung Adenocarcinoma ◽  
Immune Cells ◽  
Immune Cell ◽  
Comprehensive Analysis ◽  
Lasso Regression ◽  
Cell Functions ◽  
Qrt Pcr ◽  
Metabolic Genes

Abstract Purpose The immunotherapy of lung adenocarcinoma has received more and more attention. Different immune cells can affect other metabolic genes and lifespan, and cell metabolism directly regulates immune cell functions. Therefore, it is crucial to explore the role of immune-related metabolic genes in lung adenocarcinoma. Methods In this study, we divided immune-related metabolic genes into three categories based on different immune characteristics and researched immune and clinical pathology. LASSO regression analysis was used to screen immune-related metabolic genes, and a clinical prediction model of the screened genes was constructed. Finally, we selected the intersection of immune metabolism genes that are highly expressed in the tumor site and immune metabolism genes that are negatively related to survival, and used qRT-PCR for experimental verification. Results We first screened out immune-related metabolic genes that may affect lung cancer tumor progression, and screened out 9 pivot genes (TK1, TCN1, CAV1, ACMSD, HS3ST2, HS3ST5, AMN, ADRA2C, ACOXL) through LASSO regression analysis and constructed Prognosis model. Finally, through the screening of tumor-related immune metabolism genes, we obtained five pivot genes (HMMR, PFKP, RRM2, TCN1 and TK1). Our qRT-PCR results also show that RRM2 is positively correlated with CDK2, CDK4, CDK6, and CDK8, revealing the close relationship between RRM2 and immune cell tumor infiltration. Conclusion We conducted a comprehensive analysis of the immune infiltration of the tumor microenvironment of lung cancer, and finally determined RRM2 as a promising immune metabolism checkpoint for lung adenocarcinoma based on the high correlation of RRM2 with immune cells and CDK family.

scholarly journals Prognostic value of SEC61G in lung adenocarcinoma: a comprehensive study based on bioinformatics and in vitro validation

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qunhao Zheng ◽  
Zhiping Wang ◽  
Mengyan Zhang ◽  
Yilin Yu ◽  
Rui Chen ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Adenocarcinoma ◽  
Methylation Level ◽  
Prognostic Value ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Biological Behavior

Abstract Background Studies have shown that the Sec61 gamma subunit (SEC61G) is overexpressed in several tumors and could serve as a potential prognostic marker. However, the correlation between SEC61G and lung adenocarcinoma (LUAD) remains unclear. In the current study, we aimed to demonstrate the prognostic value and potential biological function of the SEC61G gene in LUAD. Methods Public datasets were used for SEC61G expression analyses. The prognostic value of SEC61G in LUAD was investigated using the Kaplan–Meier survival and Cox analyses. The correlation between the methylation level of SEC61G and its mRNA expression was evaluated via cBioPortal. Additionally, MethSurv was used to determine the prognostic value of the SEC61G methylation levels in LUAD. Functional enrichment analysis was conducted to explore the potential mechanism of SEC61G. Also, single sample GSEA (ssGSEA) and TIMER online tool were applied to identify the correlation between SEC61G and immune filtration. Furthermore, cell functional experiments were conducted to verify the biological behavior of SEC61G in lung adenocarcinoma cells (LAC). Results SEC61G was upregulated in pan-cancers, including LUAD. High SEC61G expression was significantly correlated with worse prognosis in LUAD patients. Multivariate analysis demonstrated that high SEC61G expression was an independent prognostic factor in the TCGA cohort. (HR = 1.760 95% CI: 1.297–2.388, p < 0.001). The methylation level of SEC61G negatively correlated with the SEC61G expression (R = − 0.290, p < 0.001), and patients with low SEC61G methylation had worse overall survival. (p = 0.0014). Proliferation-associated terms such as cell cycle and cell division were significantly enriched in GO and KEGG analysis. Vitro experiments demonstrated that knockdown of SEC61G resulted in decreased cell proliferation, invasion and facilitated apoptosis in LAC. GSEA analysis found that SEC61G expression was associated with the E2F targets. Moreover, SEC61G expression was negatively correlated with the immune cell infiltration including CD4+ T cell, CD8+ T cell, B cell, macrophage, neutrophil, and dendritic cell. Conclusion Our study indicated that overexpression of SEC61G was significantly associated with poor prognosis of LUAD patients and the malignant phenotypes of LUAD cells, suggesting that it could be a novel prognostic biomarker and potential therapeutic target of LUAD.

scholarly journals Comprehensive Analysis of the Immune and Prognostic Implication of COL6A6 in Lung Adenocarcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi Ma ◽  
Mantang Qiu ◽  
Haifa Guo ◽  
Haiming Chen ◽  
Jiawei Li ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Gene Copy ◽  
Immune Cell Infiltration ◽  
Term Survival

Collagen type VI alpha 6 chain (COL6A6), a novel collagen, has been considered as a tumor suppressor and therapeutic target in several tumors. However, the functional role of COL6A6 in immune cell infiltration and prognostic value in lung adenocarcinoma (LUAD) remains unknown. Here, we evaluated COL6A6 expression and its impact on survival among LUAD patients from The Cancer Genome Atlas (TCGA) and several other databases. COL6A6 was downregulated in LUAD tissues compared to normal tissues at both mRNA and protein levels. COL6A6 expression was negatively associated with pathological stage, tumor stage, and lymph node metastasis. High COL6A6 expression was a favorable prognostic factor in LUAD. Next, we explored the associations between COL6A6 expression and immune cell infiltration. COL6A6 expression was positively associated with the infiltration of B cells, T cells, neutrophils and dendritic cells. Additionally, the immune cell infiltration levels were associated with COL6A6 gene copy number in LUAD. Consistently, gene set enrichment analysis showed that various immune pathways were enriched in the LUAD samples with high COL6A6 expression, including pathways related to T cell activation and T cell receptor signaling. The impacts of COL6A6 on immune activity were further assessed by enrichment analysis of 50 COL6A6-associated immunomodulators. Thereafter, using Cox regression, we identified a seven-gene risk prediction signature based on the COL6A6-associated immunomodulators. The resulting risk score was an independent prognostic predictor in LUAD. Receiver operating characteristic curve analysis confirmed that the seven-gene signature had good prognostic accuracy in the TCGA-LUAD cohort and a Gene Expression Omnibus dataset. Finally, we constructed a clinical nomogram to predict long-term survival probabilities, and calibration curves verified its accuracy. Our findings highlight that COL6A6 is involved in tumor immunity, suggesting COL6A6 may be a potential immunotherapeutic target in LUAD. The proposed seven-gene signature is a promising prognostic biomarker in LUAD.

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 DNAJC10 Correlates with Tumor Immune Characteristics and Predicts the Prognosis of Glioma Patients

2021 ◽  
Author(s):  
Feng Liu ◽  
Zewei Tu ◽  
Junzhe Liu ◽  
Xiaoyan Long ◽  
Bing Xiao ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Cell ◽  
Cox Regression ◽  
Predictive Accuracy ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Time Dependent ◽  
Prognostic Role

Abstract Background: A role of DNAJC10 has been reported in several cancers, but its function in glioma is not clear. The purpose of this study was to investigate the prognostic role and the underlying functions of DNAJC10 in glioma.Methods: Reverse transcription and quantitative polymerase chain reaction and western blotting were performed to quantify the relative DNAJC10 mRNA and protein expressions of clinical samples. Wilcoxon rank sum tests were used to compare DNAJC10 expression between or among glioma subgroups with different clinicopathological features. The overall survival (OS) rates of glioma patients with different DNAJC10 expression were compared with the Kaplan-Meier method (two-sided log-rank test). The prognosis-predictive accuracy of the DNAJC10 was evaluated by time-dependent receiver operating characteristic (ROC) curves. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes annotations were conducted using the “clusterProfiler” package. Single-sample gene set enrichment analysis was used to estimate immune cell infiltrations and immune-related function levels. The independent prognostic role of DNAJC10 was determined by univariate and multivariate Cox regression analyses. A DNAJC10-based nomogram model was established using multivariate Cox regression in the R package “rms.” Results: Higher DNAJC10 expression was observed in gliomas. It was upregulated in tumors with higher World Health Organization grade, isocitrate dehydrogenase wild-type status, 1p/19q non-co-deletion, and methylguanine-DNA methyltransferase unmethylated gliomas. Patients with gliomas with higher DNAJC10 expression had poorer prognoses than those with low-DNAJC10 gliomas. The predictive accuracy of 1/3/5-year OS of DNAJC10 was stable and robust using a time-dependent ROC model. Functional enrichment analysis recognized that T cell activation and T cell receptor signaling were enriched in higher DNAJC10 gliomas. Immune cell and stromal cell infiltrations, tumor mutation burden, copy number alteration burden, and immune checkpoint genes were also positively correlated with glioma DNAJC10 expression. A DNAJ10-based nomogram model was established and showed strong prognosis-predictive ability.Conclusion: Higher DNAJC10 expression correlates with poor prognosis of patients with glioma and is a potential and useful prognostic biomarker.

scholarly journals Comprehensive Analysis of Aquaporin Superfamily in Lung Adenocarcinoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Guofu Lin ◽  
Luyang Chen ◽  
Lanlan Lin ◽  
Hai Lin ◽  
Zhifeng Guo ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Functional Enrichment Analysis ◽  
Tumor Stage ◽  
Stage I ◽  
Functional Enrichment ◽  
Gene Expressions ◽  
Kaplan Meier

Background: Lung adenocarcinoma (LUAD) is the most predomintnt lung cancer subtype with increasing morbidity and mortality. Previous studies have shown that aquaporin (AQP) family genes were correlated with tumor progression and metastasis in several kinds of malignancies. However, their biological behaviors and prognostic values in LUAD have not been comprehensively elucidated.Methods: RNA sequencing and real-time reverse transcription PCR (RT-PCR) were used to assess AQP1/3/4/5 gene expressions in LUAD patients using GEPIA and UALCAN databases. And then Kaplan–Meier analysis, cBioPortal, Metascape, GeneMANIA, TISIDB, and TIMER were utilized to determine the prognostic value, mutation frequency, and immune cell infiltration of AQP family members in LUAD.Results: We found that AQP3 expression was significantly elevated and AQP1 expression was markedly reduced in LUAD patients, whereas the expression levels of AQP4 and AQP5 exhibited no significant changes. The Kaplan–Meier survival analysis indicated that the higher expressions of AQP1/4/5 were related to longer overall survival (OS). Of interest, AQP3 was significantly correlated with the clinical tumor stage and lower AQP3 expression showed favorable prognosis in stage I LUAD patients, which indicated that AQP3 may be a potential prognostic biomarker for patients. Through functional enrichment analysis, the functions of these four AQPs genes were mainly involved in the passive transport by aquaporins, water homeostasis, and protein tetramerization. Moreover, AQP1/3/4/5 expression was strongly associated with tumor-infiltrating lymphocytes (TILs) in LUAD.Conclusion: AQP3 can be used as a prognosis and survival biomarker for stage I LUAD. These findings may provide novel insights into developing molecular targeted therapies in LUAD.

scholarly journals RNA N6-Methyladenosine Regulator-Mediated Methylation Modifications Pattern and Immune Infiltration Features in Glioblastoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Yimin Pan ◽  
Kai Xiao ◽  
Yue Li ◽  
Yuzhe Li ◽  
Qing Liu
Keyword(s):  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cell Infiltration ◽  
Immune Cell Infiltration ◽  
Lasso Regression ◽  
Gene Set Enrichment ◽  
Clinical Prognosis ◽  
Prognostic Assessment ◽  
The Relationship

Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (m6A) methylation modification reportedly plays roles in immune response. The relationship between the m6A modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential m6A modification pattern and m6A-related signatures based on 21 regulators. Thereafter, the m6A methylation modification-based prognostic assessment pipeline (MPAP) was constructed to quantitatively assess GBM patients’ clinical prognosis combining the Robustness and LASSO regression. Single-sample gene-set enrichment analysis (ssGSEA) was used to estimate the specific immune cell infiltration level. We identified two diverse clusters with diverse m6A modification characteristics. Based on differentially expressed genes (DEGs) within two clusters, m6A-related signatures were identified to establish the MPAP, which can be used to quantitatively forecast the prognosis of GBM patients. In addition, the relationship between 21 m6A regulators and specific immune cell infiltration was demonstrated in our study and the m6A regulator ELAVL1 was determined to play an important role in the anticancer response to PD-L1 therapy. Our findings indicated the relationship between m6A methylation modification patterns and tumor microenvironment immune cell infiltration, through which we could comprehensively understand resistance to multiple therapies in GBM, as well as accomplish precise risk stratification according to m6A-related signatures.

scholarly journals NPM1 Is a Prognostic Biomarker Involved in Immune Infiltration of Lung Adenocarcinoma and Associated With m6A Modification and Glycolysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xu-Sheng Liu ◽  
Lu-Meng Zhou ◽  
Ling-Ling Yuan ◽  
Yan Gao ◽  
Xue-Yan Kui ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Prognostic Biomarker ◽  
Aerobic Glycolysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Data Sets ◽  
Translational Initiation ◽  
Immune Infiltration ◽  
The Relationship

BackgroundOverexpression of NPM1 can promote the growth and proliferation of various tumor cells. However, there are few studies on the comprehensive analysis of NPM1 in lung adenocarcinoma (LUAD).MethodsTCGA and GEO data sets were used to analyze the expression of NPM1 in LUAD and clinicopathological analysis. The GO/KEGG enrichment analysis of NPM1 co-expression and gene set enrichment analysis (GSEA) were performed using R software package. The relationship between NPM1 expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets, and the relationship between NPM1 expression level and LUAD m6A modification and glycolysis was analyzed using TCGA and GEO data sets.ResultsNPM1 was overexpressed in a variety of tumors including LUAD, and the ROC curve showed that NPM1 had a certain accuracy in predicting the outcome of tumors and normal samples. The expression level of NPM1 in LUAD is significantly related to tumor stage and prognosis. The GO/KEGG enrichment analysis indicated that NPM1 was closely related to translational initiation, ribosome, structural constituent of ribosome, ribosome, Parkinson disease, and RNA transport. GSEA showed that the main enrichment pathway of NPM1-related differential genes was mainly related to mTORC1 mediated signaling, p53 hypoxia pathway, signaling by EGFR in cancer, antigen activates B cell receptor BCR leading to generation of second messengers, aerobic glycolysis and methylation pathways. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NPM1 was negatively correlated with B cells and NK cells. The TCGA and GEO data sets analysis indicated that the NPM1 expression was significantly correlated with one m6A modifier related gene (YTHDF2) and five glycolysis related genes (ENO1, HK2, LDHA, LDHB and SLC2A1).ConclusionNPM1 is a prognostic biomarker involved in immune infiltration of LUAD and associated with m6A modification and glycolysis. NPM1 can be used as an effective target for diagnosis and treatment of LUAD.

scholarly journals Combined Analysis of ceRNA Regulatory Network and DNA Methylation in CAD

2021 ◽  
Author(s):  
Yue Zhao ◽  
Chen Wang ◽  
Wangxia Li ◽  
Bingyu Jin ◽  
Yang Xiang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Clinical Samples ◽  
Gene Expressions ◽  
Qrt Pcr ◽  
Cerna Network ◽  
Differentially Methylated Genes

Abstract BackgroundThe mobidity and mortality of coronary artery disease (CAD) is increasing year by year. Hence it is urgent to probe into the molecular mechanism of CAD and seek new therapeutic strategies. The purpose of our study was to screen genes associated with the development of CAD by using bioinformatics tools and clinical samples. MethodsMicroarray datasets from the Gene Expression Omnibus (GEO) database of peripheral blood cells (PBLs) were chosen for this study, and candidate differentially expressed microRNAs (DEMs) were screened using the limma and weighted co-expression network analysis (WGCNA) packages in R (v4.0). Subsequently, we construct a competitive endogenous RNAs (ceRNA) network and perform enrichment analysis of genes in the network. Meanwhile, differentially methylated genes (DMGs) in PBLs were identified using the "ChAMP" package in a DNA methylation chip. We then constructed the methylation-associated ceRNA network in CAD. Eventually, the methylation levels of genes and the relationship with the expression of genes in ceRNA were validated in PBLs samples using the Illumina Methylation 850K chip and transcriptome sequencing, while gene expressions were verified by qRT-PCR. And the regulation of DNA methylation on gene expression was verified in the THP-1 cells treated with 5-Aza-2'-deoxycytidine (5-AZA). ResultsA total of 71 differentially expressed miRNAs were screened by both WGCNA and limma. Then the ceRNA network in CAD was constructed with 269 nodes and 705 edges, which were significantly enriched in the chemokine-mediated signaling pathway and so on. Furthermore, from 4354 identified DMGs in a methylation data, 34 methylation-associated differentially expressed genes (DEGs) and 1 differentially expressed lncRNA (DEL) were obtained. After verification of methylation experiments in study population A, three genes were found to have altered methylation consistent with the bioinformatics results. And these genes were correlated in terms of methylation and expression levels. Corresponding with the bioinformatics results, qRT-PCR results in validation set B also showed that the expression of AGPAT4 and FAM169A were significantly lower in CAD. In addition, 5-AZA treatment could increase the expression of AGPAT4 and FAM169A in THP-1 cells. ConclusionsOur study deepens the understanding of the molecular mechanisms underlying the pathogenesis of CAD and provides new ideas for its treatment.

scholarly journals Higher cytolytic score correlates with an immunosuppressive tumor microenvironment and reduced survival in glioblastoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexander F. Haddad ◽  
Jia-Shu Chen ◽  
Taemin Oh ◽  
Matheus P. Pereira ◽  
Rushikesh S. Joshi ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Cell ◽  
Cell Types ◽  
Cd8 T Cell ◽  
The Cancer Genome Atlas ◽  
Cell Infiltration ◽  
Sequencing Data ◽  
Gene Score ◽  
T Cell Infiltration ◽  
The Relationship

Abstract Cytolytic score (CYT), calculated from mRNA expression levels of granzyme and perforin, positively correlates with CD8+ T cell infiltration/activity in a variety of cancers. Unlike other cancers, higher CYT has been associated with worse prognosis in glioblastoma (GBM). To address this discrepancy, we sought to investigate the relationship between CYT and immune checkpoint gene score (ICGscore), as well as their correlation with patient survival and tumor immune cell infiltration. Clinical and RNA-sequencing data for patients with newly diagnosed GBM were obtained from The Cancer Genome Atlas. Maximally-selected rank statistics was used to dichotomize subgroups. CIBERSORT was used to estimate abudence of immune cell-types. Spearman correlation was used to characterize the relationship between CYT and ICGscore. Kaplan–Meier curves were generated for survival analysis. Overall, 28/151 patients had high CYT. High CYT was associated with a mesenchymal subtype (p < 0.001) and worse survival (7.45 vs. 12.2 months, p < 0.001). There were no differences in patient demographics, IDH/MGMT mutation status, or treatment. On subgroup analysis, patients with high CYT/ICGscore had significantly increased CD8+ infiltration (p < 0.001), as expected, and worse survival (HR 0.445, p < 0.01). Furthermore, CYT strongly correlated with ICGscore (RS = 0.675, p < 0.001). The high CYT/ICGscore subgroup was associated with greater infiltration of M2 macrophages (p = 0.011) and neutrophils (p = 0.055). Our study highlights a multidimensional immunosuppressive GBM microenvironment in patients with higher CYT and potentially identifies patients with high CYT/ICGscore as a subgroup that may particularly benefit from multi-faceted immunotherapies, given their already elevated tumor CD8+ T cell levels.

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