scholarly journals Analysis of the Expression and Prognostic Value of MSH2 in Pan-Cancer Based on Bioinformatics

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Wenli Qiu ◽  
Ke Ding ◽  
Lusheng Liao ◽  
Yongchang Ling ◽  
Xiaoqiong Luo ◽  
...  
Keyword(s):  
T Cells ◽  
Prognostic Value ◽  
Cox Regression ◽  
Cancer Susceptibility ◽  
Prognostic Significance ◽  
Housekeeping Gene ◽  
Significant Negative Correlation ◽  
Immune Infiltration ◽  
Potential Biomarker ◽  
Pan Cancer

Background. MutS homolog 2 (MSH2), with the function of identifying mismatches and participating in DNA repair, is the “housekeeping gene” in the mismatch repair (MMR) system. MSH2 deficiency has been reported to enhance cancer susceptibility for the association of hereditary nonpolyposis colorectal cancer. However, the expression and prognostic significance of MSH2 have not been studied from the perspective of pan-cancer. Methods. The GTEx database was used to analyze the expression of MSH2 in normal tissues. The TCGA database was used to analyze the differential expression of MSH2 in pan-cancers. The prognostic value of MSH2 in pan-cancer was assessed using Cox regression and Kaplan-Meier analysis. Spearman correlations were used to measure the relationship between the expression level of MSH2 in pan-cancer and the level of immune infiltration, tumor mutational burden (TMB), and microsatellite instability (MSI). Results. MSH2 is highly expressed in most type of cancers and significantly correlated with prognosis. In COAD, KIRC, LIHC, and SKCM, the expression of MSH2 was significantly positively correlated with the abundance of B cells, CD4+ T cells, CD8+ T cells, dendritic cells, macrophages, and neutrophils. In THCA, MSH2 expression correlated with CD8+T Cell showed a significant negative correlation. MSH2 had significantly negative correlations with stromal score and immune score in a variety of cancers and significantly correlated with TMB and MSI of a variety of tumors. Conclusions. MSH2 may play an important role in the occurrence, development, and immune infiltration of cancer. MSH2 can emerge as a potential biomarker for cancer diagnosis and prognosis.

scholarly journals Identification of CDC20 As an Immune Infiltration-Correlated Prognostic Biomarker in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Chen Xiong ◽  
Zhihuai Wang ◽  
Guifu Wang ◽  
Chi Zhang ◽  
Shengjie Jin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Poor Prognosis ◽  
Prognostic Value ◽  
Cox Regression ◽  
Cancer Genome ◽  
Regression Analyses ◽  
Ubiquitin Protein Ligase ◽  
Immune Infiltration

Abstract Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. Some E3 ubiquitin-protein ligases play essential roles in HCC development. We aimed to explore a hub E3 ubiquitin-protein ligase gene and verify its association with prognosis and immune cell infiltration in HCC. We identified cell division cycle 20 (CDC20) as a hub E3 ubiquitin-protein ligase in HCC by determining the intersecting genes in a protein-protein interaction (PPI) network of differentially expressed genes (DEGs) in HCC data from the International Cancer Genome Consortium (ICGC) and 919 E3 ubiquitin-protein ligase genes from the Integrated annotations for Ubiquitin and Ubiquitin-like Conjugation Database (IUUCD). DEGs and their correlations with clinicopathological features were explored in The Cancer Genome Atlas (TCGA), ICGC, and Gene Expression Omnibus (GEO) databases via the Wilcoxon signed-rank test. The prognostic value of CDC20 was illustrated by Kaplan-Meier (K-M) curves and Cox regression analyses. Subsequently, the correlation between CDC20 and immune infiltration was demonstrated via the Tumor Immune Estimation Resource (TIMER) and Gene Expression Profiling Interactive Analysis (GEPIA). CDC20 expression was significantly higher in HCC than in normal tissues (all P < 0.05). K-M curves and Cox regression analyses showed that high CDC20 expression predicted a poor prognosis and might be an independent risk factor for HCC prognosis (P < 0.05). Additionally, the TIMER and GEPIA results indicated that CDC20 is correlated with the immune infiltration of CD8 + T cells, T cells (general), monocytes, and exhausted T cells. This research revealed the potential prognostic value of CDC20 in HCC and demonstrated that CDC20 might be an immune-associated therapeutic target in HCC because of its correlation with immune infiltration.

scholarly journals CD96 Correlates With Immune Infiltration and Impacts Patient Prognosis: A Pan-Cancer Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenrui Ye ◽  
Cong Luo ◽  
Fangkun Liu ◽  
Zhixiong Liu ◽  
Fenghua Chen
Keyword(s):  
T Cells ◽  
Nk Cells ◽  
Protective Factor ◽  
Immune Checkpoints ◽  
Lower Grade ◽  
Immune Infiltration ◽  
Potential Biomarker ◽  
Cancer Types ◽  
Patient Prognosis ◽  
Pan Cancer

BackgroundImmunotherapy has significantly improved patient outcomes, but encountered obstacles recently. CD96, a novel immune checkpoint expressed on T cells and natural killer (NK) cells, is essential for regulating immune functions. However, how CD96 correlating with immune infiltration and patient prognosis in pan-cancer remains unclear.MethodsHPA, TCGA, GEO, GTEx, Oncomine, TIMER2.0, PrognoScan, Linkedomics, Metascape, and GEPIA2 databases were used to analyze CD96 in cancers. Visualization of data was mostly achieved by R language, version 4.0.2.ResultsIn general, CD96 was differentially expressed between most cancer and adjacent normal tissues. CD96 significantly impacted the prognosis of diverse cancers. Especially, high CD96 expression was associated with poorer overall survival (OS) and disease-specific survival (DSS) in the TCGA lower grade glioma (LGG) cohort (OS, HR = 2.18, 95% CI = 1.79–2.66, P &lt; 0.001). The opposite association was significantly observed in skin cutaneous melanoma (SKCM) cohort (OS, HR = 0.96, 95% CI = 0.94–0.98, P &lt; 0.001). Notably, SKCM samples demonstrated the highest CD96 mutation frequency among all cancer types. Furthermore, in most cancers, CD96 expression level was significantly correlated with expression levels of recognized immune checkpoints and abundance of multiple immune infiltrates including CD8+ T cells, dendric cells (DCs), macrophages, monocytes, NK cells, neutrophils, regulatory T cells (Tregs), and follicular helper T cells (Tfh). CD96 was identified as a risk factor, protective factor, and irrelevant variable in LGG, SKCM and adrenocortical carcinoma (ACC), respectively. CD96 related genes were involved in negative regulation of leukocyte in LGG, however, involved in multiple positive immune processes in SKCM. Furthermore, CD96 was significantly associated with particular immune marker subsets. Importantly, it strongly correlated with markers of type 1 helper T cell (Th1) in SKCM, but not in LGG or ACC either.ConclusionsCD96 participates in diverse immune responses, governs immune cell infiltration, and impacts malignant properties of various cancer types, thus standing as a potential biomarker for determining patient prognosis and immune infiltration in multiple cancers, especially in glioma and melanoma.

scholarly journals EVA1B to Evaluate the Tumor Immune Microenvironment and Clinical Prognosis in Glioma

2021 ◽  
Vol 12 ◽  
Author(s):  
Shanqiang Qu ◽  
Jin Liu ◽  
Huafu Wang
Keyword(s):  
T Cells ◽  
B Cells ◽  
Immune Cells ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Area Under The Curve ◽  
Biological Databases ◽  
Clinical Prognosis ◽  
Immune Infiltration ◽  
Potential Biomarker

BackgroundPrevious research indicated that the tumor cells and microenvironment interactions are critical for the immunotherapeutic response. However, predicting the clinical response to immunotherapy remains a dilemma for clinicians. Hence, this study aimed to investigate the associations between EVA1B expression and prognosis and tumor-infiltrating immune cells in glioma.MethodsFirstly, we detected the EVA1B expression in glioma tissues through biological databases. The chi-squared test, Kaplan-Meier, and univariate and multivariate Cox regression analyses were used to analyze the clinical significance of EVA1B expression. The correlation between EVA1B expression and levels of tumor-infiltrating immune cells in glioma tissues was investigated. Receiver operating characteristic (ROC) analysis was performed to compare the predictive power between EVA1B and other commonly immune-related markers.ResultsIn the CGGA cohort of 325 glioma patients, we found that EVA1B was upregulated in glioma, and increased with tumor grade. High EVA1B expression was prominently associated with unfavorable clinicopathological features, and poorer survival of patients, which were further confirmed by TCGA (n=609) and GEO (n=74) cohorts. Furthermore, multivariate analysis indicated that EVA1B is an independent prognostic biomarker for glioma. Importantly, EVA1B overexpression was associated with a higher infiltration level of CD4+ T cells, CD8+ T cells, B cells, macrophages, and neutrophils in glioma. ROC curves showed that, compared with PD-L1, CTLA-4, and Siglec15, EVA1B presented a higher area under the curve (AUC) value (AUC=0.824) for predicting high immune infiltration levels in glioma.ConclusionsWe found that EVA1B was upregulated and could act as a poor prognostic biomarker in glioma. Importantly, EVA1B overexpression was associated with the immune infiltration levels of immune cells including B cells, CD4+ T cells, CD8+ T cells, macrophages, and neutrophils, and strongly with the overall immune infiltration levels of glioma. These findings suggested that EVA1B might be a potential biomarker for evaluating prognosis and immune infiltration in glioma.

scholarly journals Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yunfeng Xu ◽  
Ze Zhang ◽  
Da Xu ◽  
Xin Yang ◽  
Lina Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Panel ◽  
Metabolic Reprogramming ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Immune Infiltration

Abstract Background Cumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment. Methods We compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n  =  28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n  =  60) and TCGA (n  =  411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan–Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY. Results We identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC.ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application. Conclusions We investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.

scholarly journals Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

2021 ◽  
Author(s):  
Yunfeng Xu ◽  
Ze Zhang ◽  
Da Xu ◽  
Li-Na Zhou ◽  
Ying Zhu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Gene Panel ◽  
Metabolic Reprogramming ◽  
Immune Checkpoints ◽  
Immune Microenvironment ◽  
Immune Infiltration

Abstract BackgroundCumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment.MethodsWe compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n = 28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n = 60) and TCGA (n = 411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms (TIMER, CIBERSORT, quanTIseq, xCell, MCP-counter, EPIC) and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan-Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY.ResultsWe identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC. According to the survival outcome and correlation analysis, ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application.ConclusionsWe investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.

scholarly journals Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

2022 ◽  
Vol 8 ◽  
Author(s):  
Fei Chen ◽  
Yumei Fan ◽  
Xiaopeng Liu ◽  
Jianhua Zhang ◽  
Yanan Shang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathways ◽  
Immune Cells ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Clinicopathological Parameters ◽  
Immune Infiltration ◽  
Cancer Types ◽  
The Relationship ◽  
Pan Cancer

Heat shock factor 2 (HSF2), a transcription factor, plays significant roles in corticogenesis and spermatogenesis by regulating various target genes and signaling pathways. However, its expression, clinical significance and correlation with tumor-infiltrating immune cells across cancers have rarely been explored. In the present study, we comprehensively investigated the expression dysregulation and prognostic significance of HSF2, and the relationship with clinicopathological parameters and immune infiltration across cancers. The mRNA expression status of HSF2 was analyzed by TCGA, GTEx, and CCLE. Kaplan-Meier analysis and Cox regression were applied to explore the prognostic significance of HSF2 in different cancers. The relationship between HSF2 expression and DNA methylation, immune infiltration of different immune cells, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed using data directly from the TCGA database. HSF2 expression was dysregulated in the human pan-cancer dataset. High expression of HSF2 was associated with poor overall survival (OS) in BRCA, KIRP, LIHC, and MESO but correlated with favorable OS in LAML, KIRC, and PAAD. The results of Cox regression and nomogram analyses revealed that HSF2 was an independent factor for KIRP, ACC, and LIHC prognosis. GO, KEGG, and GSEA results indicated that HSF2 was involved in various oncogenesis- and immunity-related signaling pathways. HSF2 expression was associated with TMB in 9 cancer types and associated with MSI in 5 cancer types, while there was a correlation between HSF2 expression and DNA methylation in 27 types of cancer. Additionally, HSF2 expression was correlated with immune cell infiltration, immune checkpoint genes, and the tumor immune microenvironment in various cancers, indicating that HSF2 could be a potential therapeutic target for immunotherapy. Our findings revealed the important roles of HSF2 across different cancer types.

scholarly journals A genomic mutation signature predicts the clinical outcomes of immunotherapy and characterizes immunophenotypes in gastrointestinal cancer

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Xi Jiao ◽  
Xin Wei ◽  
Shuang Li ◽  
Chang Liu ◽  
Huan Chen ◽  
...  
Keyword(s):  
Gastrointestinal Cancer ◽  
Prognostic Value ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Cancer Center ◽  
Genomic Profile ◽  
Prognostic Signature ◽  
Powerful Predictor ◽  
Potential Biomarker ◽  
Peking University

AbstractThe association between genetic variations and immunotherapy benefit has been widely recognized, while such evidence in gastrointestinal cancer remains limited. We analyzed the genomic profile of 227 immunotherapeutic gastrointestinal cancer patients treated with immunotherapy, from the Memorial Sloan Kettering (MSK) Cancer Center cohort. A gastrointestinal immune prognostic signature (GIPS) was constructed using LASSO Cox regression. Based on this signature, patients were classified into two subgroups with distinctive prognoses (p < 0.001). The prognostic value of the GIPS was consistently validated in the Janjigian and Pender cohort (N = 54) and Peking University Cancer Hospital cohort (N = 92). Multivariate analysis revealed that the GIPS was an independent prognostic biomarker. Notably, the GIPS-high tumor was indicative of a T-cell-inflamed phenotype and immune activation. The findings demonstrated that GIPS was a powerful predictor of immunotherapeutic survival in gastrointestinal cancer and may serve as a potential biomarker guiding immunotherapy treatment decisions.

scholarly journals The expression of miR-211-5p in atherosclerosis and its influence on diagnosis and prognosis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanxia Zhang ◽  
Huiyun Wang ◽  
Yu Xia
Keyword(s):  
Roc Curve ◽  
Cox Regression ◽  
Survival Curve ◽  
Prognostic Significance ◽  
Significant Negative Correlation ◽  
Diagnostic Value ◽  
Expression Level ◽  
Healthy Controls ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis

Abstract Background The purpose of this study was to evaluate the diagnostic and prognostic significance of miR-211-5p in atherosclerosis (AS) by detecting the expression level in serum of patients with AS. Methods A total of 85 healthy controls and 90 asymptomatic AS patients participated in this study. The expression level of miR-211-5p in all subjects were measured by qRT-PCR. Spearman correlation coefficient was used to evaluate the correlation of miR-211-5p with CRP and CIMT. The ROC curve was established to assess the diagnostic value of miR-211-5p in AS. The Kaplan–Meier survival curve and multivariate COX regression analysis were used to evaluate the prognostic significance of miR-211-5p in AS. Results The expression levels of miR-211-5p in AS patients were significantly lower than in healthy controls (P < 0.001), and miR-211-5p showed a significant negative correlation with CRP (r =  − 0.639, P < 0.001) and CIMT (r =  − 0.730, P < 0.001). The AUC of the ROC curve was 0.900, the specificity and the sensitivity were 84.7% and 78.9%, respectively, which indicating that miR-211-5p had diagnostic value for AS. Survival analysis showed that patients with low miR-211-5p expression were more likely to have cardiovascular end-point events (Log rank P = 0.013). Conclusion Serum miR-211-5p could be used as a new biomarker for the diagnosis of AS, and the low expression of miR-211-5p is associated with the poor prognosis of AS.

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>

ERO1L shapes the immune-suppressive tumor microenvironment and is a potential biomarker for immunotherapy response in lung adenocarcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21006-e21006
Author(s):  
Lihui Liu ◽  
Chao Wang ◽  
Sini Li ◽  
Pei Xue ◽  
Hua Bai ◽  
...  
Keyword(s):  
T Cells ◽  
Endoplasmic Reticulum ◽  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
Survival Data ◽  
Checkpoint Inhibitors ◽  
Q Value ◽  
Immune Infiltration ◽  
Potential Biomarker

e21006 Background: Recently, immune checkpoint inhibitors have led to a paradigm shift in treatment for patients with lung adenocarcinoma (LUAD), however, the identification of biomarkers to enable patient selection is urgently required. The endoplasmic reticulum oxidoreductin-1-like ( ERO1L) gene encodes an endoplasmic reticulum luminal localized glycoprotein known to associated with hypoxia. The role of ERO1L in the crafting of the tumor immune microenvironment (TIME) is yet to be elucidated. Methods: In this study, raw datasets (including RNA-seq, methylation, sgRNA-seq, phenotype, and survival data) were obtained from public databases. This data was analyzed and used to explore the biological landscape of ERO1L in immune infiltration. Expression data was used to characterize samples. Using gene signatures and cell quantification, stromal and immune infiltration was determined. These findings were used to predict sensitivity to immunotherapy. Results: We identified ERO1L to be an oncogene, the mRNA expression of which is significantly higher in LUAD compared with normal tissues. High expression levels of ERO1L were associated with poor prognoses in terms of overall survival (HR: 1.52, 95% CI: 1.27-1.82) and progression-free survival (HR: 1.93, 95% CI: 1.47-2.53). This overexpression was found to be a result of hypomethylation of the ERO1L promoter. Overexpression of ERO1L resulted in an immune-suppressive TIME via the recruitment of immune-suppressive cells including regulatory T cells (Spearman’s ρ = 0.199, p < 0.001) cancer associated fibroblasts (ρ = 0.286, p < 0.001), and myeloid-derived suppressor cells (ρ = 0.423, p < 0.001), and also indicated the polarization of M1-type to M2-type macrophage. On the contrary, overexpression of ERO1L was closely associated with deficiency of immune-active cells including B cells (ρ = -0.250, p < 0.001), CD8+ T cells (ρ = -0.299, p < 0.001), and NK cells (ρ = -0.258, p < 0.001). Using the Tumor Immune Dysfunction and Exclusion (TIDE) framework, it was identified that patients in the ERO1Lhigh group possessed a significantly lower response rate (31.0%) to immunotherapy compared with the ERO1Llow group (86.0%). Mechanistic analysis revealed that overexpression of ERO1L was associated with the upregulation of JAK-STAT (NES = 1.65, FDR q-value = 0.0) and NF-κB (NES = 2.03, FDR q-value = 0.0) signaling pathways, thus affecting chemokine and cytokine patterns in the TIME. Conclusions: Our study provides clear insight into the potential role of ERO1L in tumor immunology. Overexpression of ERO1L was indicative of a hypoxia-induced immune-suppressive TIME, which was shown to confer resistance to immunotherapy in patients with LUAD. ERO1L was shown to mediate cytokine and chemokine patterns in the TIME, which were resulted from activations of JAK-STAT and NF-κB signaling pathways.

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