scholarly journals FURIN correlated with immune infiltration serves as a potential biomarker in SARS-CoV-2 infection-related lung adenocarcinoma

2021 ◽  
Author(s):  
Lianxiang Luo ◽  
Manshan Li ◽  
Jiating Su ◽  
Xinyue Yao ◽  
Hui Luo
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Gene Expression Omnibus ◽  
Poor Overall Survival ◽  
Immune Infiltration ◽  
Interactive Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Human Protein Atlas

Abstract FURIN, as a proprotein convertase, has been found to be expressed in a variety of cancers and plays an important role in cancer. In addition, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) requires FURIN to enter human cells. However, the role of FURIN in lung adenocarcinoma remains unclear. And the expression of SARS-CoV-2 related gene in lung adenocarcinoma has not been clarified. Therefore, in order to explore the prognostic value and mechanism of FURIN in lung adenocarcinoma, we performed bioinformatics analysis with Oncomine, TIMER (Tumor Immune Estimation Resource), GEPIA (Gene Expression Profiling Interactive Analysis), HPA (human protein atlas), UALCAN, PrognoScan, Kaplan-Meier plotter, cBioPortal, and LinkedOmics databases. And then We used GSE44274 in the GEO (Gene Expression Omnibus) database to analyze the expression of FURIN in LUAD patients who infected with SARS-CoV. FURIN was highly expressed in lung adenocarcinoma and was significantly associated with poor overall survival. FURIN expression was found to be correlated with six major permeable immune cells and with macrophage immune marker in LUAD patients. In addition, SARS-CoV-2 infection might affect the expression of FURIN. FURIN can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.

scholarly journals FURIN Correlated with Immune Infiltration Serves as a Potential Biomarker in SARS-CoV-2 Infection-Related Lung Adenocarcinoma

2021 ◽  
Author(s):  
Lianxiang Luo ◽  
Manshan Li ◽  
Jiating Su ◽  
Xinyue Yao ◽  
Hui Luo
Keyword(s):  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Clinical Feature ◽  
Related Gene ◽  
Poor Overall Survival ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Kaplan Meier Plotter

Abstract Background: FURIN, as a proprotein invertase, has been found to be expressed in a variety of cancers and plays an important role in cancer. In addition, SARS-CoV-2 requires FURIN to enter human cell. However, the role of FURIN in lung adenocarcinoma remains unclear. And the expression of SARS-CoV-2 related gene in lung adenocarcinoma have not been clarify. Methods: In this study, we obtained the expression data of Oncomine, TIMER, GEPIA, HPA. Then we used UALCAN database to analyze the expression of FURIN in different clinical feature subgroups. In PrognoScan and Kaplan-Meier plotter databases, we found a certain association between FURIN and poor OS outcomes in LUAD patients. Then we used the cBioPortal database to determine the type and frequency of FURIN changes in LUAD patients. Studies based on the TIMER database show a strong correlation between FURIN expression and various immune cell infiltrates and markers. Analysis in UALCAN database showed that the decreased promoter methylation level of FURIN in LUAD may lead to the high expression of FURIN. Furthermore, we used the LinkedOmics database to evaluate gene co-expression of FURIN in LUAD and to investigate their role in tumor immunity. Finally, we evaluated the expression of FURIN in LUAD patients who infected with SARS-CoV.Results: FURIN was highly expressed in lung adenocarcinoma. And FURIN expression was significantly associated with poor overall survival. FURIN expression was found to be correlated with six major permeable immune cells and with macrophage immune marker in LUAD patients. In addition, SARS-CoV-2 infection might affect the expression of FURIN. Conclusions: FURIN, as SARS-CoV-2 related gene, was highly expressed in LUAD. Furthermore, FURIN can be used as a promising biomarker for determining prognosis and immune infiltration in LUAD patients.

scholarly journals Identification of key genes associated with lung adenocarcinoma by bioinformatics analysis

2021 ◽  
Vol 104 (1) ◽  
pp. 003685042199727
Author(s):  
Xinyu Wang ◽  
Jiaojiao Yang ◽  
Xueren Gao
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Tumor Stage ◽  
Gene Expression Omnibus ◽  
Poor Overall Survival ◽  
Key Genes ◽  
Low Expression

Lung adenocarcinoma (LUAD) is the most common histological type of lung cancer, comprising around 40% of all lung cancer. Until now, the pathogenesis of LUAD has not been fully elucidated. In the current study, we comprehensively analyzed the dysregulated genes in lung adenocarcinoma by mining public datasets. Two sets of gene expression datasets were obtained from the Gene Expression Omnibus (GEO) database. The dysregulated genes were identified by using the GEO2R online tool, and analyzed by R packages, Cytoscape software, STRING, and GPEIA online tools. A total of 275 common dysregulated genes were identified in two independent datasets, including 54 common up-regulated and 221 common down-regulated genes in LUAD. Gene Ontology (GO) enrichment analysis showed that these dysregulated genes were significantly enriched in 258 biological processes (BPs), 27 cellular components (CCs), and 21 molecular functions (MFs). Furthermore, protein-protein interaction (PPI) network analysis showed that PECAM1, ENG, KLF4, CDH5, and VWF were key genes. Survival analysis indicated that the low expression of ENG was associated with poor overall survival (OS) of LUAD patients. The low expression of PECAM1 was associated with poor OS and recurrence-free survival of LUAD patients. The cox regression model developed based on age, tumor stage, ENG, PECAM1 could effectively predict 5-year survival of LUAD patients. This study revealed some key genes, BPs, CCs, and MFs involved in LUAD, which would provide new insights into understanding the pathogenesis of LUAD. In addition, ENG and PECAM1 might serve as promising prognostic markers in LUAD.

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.

scholarly journals The role of FOXD2-AS1 in cancer: a comprehensive study based on data mining and published articles

2020 ◽  
Vol 40 (11) ◽  
Author(s):  
Yongping Zhang ◽  
Chaojie Liang ◽  
Yu Zhang ◽  
Zhinmin Wang ◽  
Ruihuan Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Patients ◽  
Tumor Size ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Gene Expression Omnibus ◽  
Tnm Stage ◽  
Potential Biomarker ◽  
Tcga Dataset

Abstract Background and aims: Long non-coding RNA (lncRNA) FOXD2 adjacent opposite strand RNA 1 (FOXD2-AS1) is aberrantly expressed in various cancers and associated with cancer progression. A comprehensive meta-analysis was performed based on published literature and data in the Gene Expression Omnibus database, and then the Cancer Genome Atlas (TCGA) dataset was used to assess the clinicopathological and prognostic value of FOXD2-AS1 in cancer patients. Methods: Gene Expression Omnibus databases of microarray data and published articles were used for meta-analysis, and TCGA dataset was also explored using the GEPIA analysis program. Hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the role of FOXD2-AS1 in cancers. Results: This meta-analysis included 21 studies with 2391 patients and 25 GEO datasets with 3311 patients. The pooled HRs suggested that highly expressed FOXD2-AS1 expression was correlated with poor overall survival (OS) and disease-free survival (DFS). Similar results were obtained by analysis of TCGA data for 9502 patients. The pooled results also indicated that FOXD2-AS1 expression was associated with bigger tumor size and advanced TNM stage, but was not related to age, gender, differentiation and lymph node metastasis. Conclusion: The present study demonstrated that FOXD2-AS1 is closely related to tumor size and TNM stage. Additionally, increased FOXD2-AS1 was a risk factor of OS and DFS in cancer patients, suggesting FOXD2-AS1 may be a potential biomarker in human cancers.

scholarly journals Comprehensive Analysis of Clinical Significance, Immune Infiltration and Biological Role of m6A Regulators in Early-Stage Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Bolun Zhou ◽  
Shugeng Gao
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Early Stage ◽  
Adoptive T Cell Therapy ◽  
Predictive Score ◽  
Poor Overall Survival ◽  
T Cell Therapy ◽  
Immune Infiltration ◽  
Mutation Burden

Recent publications have revealed that N6-methyladenosine (m6A) modification is critically involved in tumorigenesis and metastasis. However, the correlation of m6A modification and immune infiltration in early-stage lung adenocarcinoma (LUAD) is still uncertain. We performed NMF clustering based on 23 m6A regulators and identify three distinct m6A clusters and three m6A related genes clusters (m6A cluster-R) in early-stage LUAD. The immune infiltrating levels were calculated using CIBERSORT, MCPcounter and ssGSEA algorithms. And we established the m6A-predictive score to quantify m6A modified phenotypes and predict immunotherapeutic responses. Based on the TME characteristics, different immune profiles were also identified among three m6A gene-related clusters. And the m6A-R-C2 was related to a favorable overall survival (OS), whereas m6A-R-C3 had unfavorable overall survival. The m6A-predictive score was built according to the expression levels of m6A-related genes, and patients could be stratified into subgroups with low/high scores. Patients with high scores had poor overall survival, enhanced immune infiltration, high tumor mutation burden and increased level of somatic mutation. Besides, patients with high scores had unfavorable overall survival in the anti-PD-1 cohort, whereas the overall survival of high-score patients was better in the adoptive T cell therapy cohort. Our work highlights that m6A modification is closely related to immune infiltration in early-stage LUAD, which also contributes to the development of more effective immunotherapy strategies.

scholarly journals IL-11RA is a Prognostic Biomarker and Correlated with Immune Infiltration in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Aitao Nai ◽  
SHOAIB BASHIR ◽  
Ling Jin ◽  
Zirui He ◽  
Shuwen Zeng ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Clinicopathological Parameters ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
Potential Biomarker

Abstract Background: Interleukin-11 receptor subunit alpha (IL-11RA) contributes to multiple biological processes in various tumors. However, the role of IL-11RA in Lung adenocarcinoma (LUAD) is still undetermined. The study aims to explore the role of IL-11RA in LUAD via an integrated bioinformatics analysis. Methods: TIMER, GEPIA, TCGA and HPA databases analysis were used to detect IL-11RA expression. UALCAN database was used to analysis the correlation between IL-11RA expression and clinicopathological parameters of LUAD. Kaplan-Meier Plotter, TCGA and GEO databases were used to analysis overall survival (OS) and progression-free survival (PFS) of the LUAD patients. Univariate Cox regression analysis was used to assess the prognostic value of IL-11RA in different clinical characteristics. GSEA, and TIMER were used to investigate the relationship between IL-11RA and immune infiltration.Results: The expression of IL-11RA was down-regulated in LUAD tissues. Furthermore, IL-11RA expression was closely associated with clinical stage, lymph node stage and smoking habits. The patients with lower IL-11RA expression had poorer overall survival (OS) and progression-free survival (PFS). Lower IL-11RA expression was significantly associated with its hypermethylation, and the hypermethylation of CpG site at cg14609668 and cg21504624 was obviously correlated with poorer OS. Then, we found that IL-11RA may play an important role in LUAD progression and immune regulations. Notably, High expression of IL-11RA may suppress the progression of LUAD through inhibiting cell proliferation and immune cell infiltration, especially in B cells, CD4+ T cells, and Dendritic Cell. Conclusions: Decreased IL-11RA expression correlates with poor prognosis and immune infiltration in LUAD. Our work highlights IL-11RA might be a potential biomarker for prognosis and provide a new therapeutic target for LUAD patients.

scholarly journals Identification and Validation of a Novel Immune-Related Four-lncRNA Signature for Lung Adenocarcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Jixin Wang ◽  
Xiangjun Yin ◽  
Yin-Qiang Zhang ◽  
Xuming Ji
Keyword(s):  
Gene Expression ◽  
Lung Adenocarcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Lasso Regression ◽  
Kaplan Meier

Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, the prognosis of patients with which is associated with both lncRNAs and cancer immunity. In this study, we collected gene expression data of 585 LUAD patients from The Cancer Genome Atlas (TCGA) database and 605 subjects from the Gene Expression Omnibus (GEO) database. LUAD patients were divided into high and low immune-cell-infiltrated groups according to the single sample gene set enrichment analysis (ssGSEA) algorithm to identify differentially expressed genes (DEGs). Based on the 49 immune-related DE lncRNAs, a four-lncRNA prognostic signature was constructed by applying least absolute shrinkage and selection operator (LASSO) regression, univariate Cox regression, and stepwise multivariate Cox regression in sequence. Kaplan–Meier curve, ROC analysis, and the testing GEO datasets verified the effectiveness of the signature in predicting overall survival (OS). Univariate Cox regression and multivariate Cox regression suggested that the signature was an independent prognostic factor. The correlation analysis revealed that the infiltration immune cell subtypes were related to these lncRNAs.

scholarly journals ERO1L Is a Novel and Potential Biomarker in Lung Adenocarcinoma and Shapes the Immune-Suppressive Tumor Microenvironment

2021 ◽  
Vol 12 ◽  
Author(s):  
Lihui Liu ◽  
Chao Wang ◽  
Sini Li ◽  
Yan Qu ◽  
Pei Xue ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Suppressor Cells ◽  
Immune Infiltration ◽  
Mechanistic Analysis ◽  
Potential Biomarker ◽  
Lower Response Rate ◽  
Tumor Immune Microenvironment

BackgroundThe endoplasmic reticulum oxidoreductin-1-like (ERO1L) gene encodes an endoplasmic reticulum luminal localized glycoprotein known to associated with hypoxia, however, the role of ERO1L in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in lung adenocarcinoma (LUAD).MethodsIn 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.ResultsThis study found that ERO1L was significantly overexpressed in LUAD in comparison to normal tissue. 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 (Tregs), cancer associated fibroblasts, M2-type macrophages, and myeloid-derived suppressor cells. Using the Tumor Immune Dysfunction and Exclusion (TIDE) framework, it was identified that patients in the ERO1Lhigh group possessed a significantly lower response rate to immunotherapy in comparison to the ERO1Llow group. Mechanistic analysis revealed that overexpression of ERO1L was associated with the upregulation of JAK-STAT and NF-κB signaling pathways, thus affecting chemokine and cytokine patterns in the TIME.ConclusionsThis study found that overexpression of ERO1L was associated with poor prognoses in patients with LUAD. Overexpression of ERO1L was indicative of a hypoxia-induced immune-suppressive TIME, which was shown to confer resistance to immunotherapy in patients with LUAD. Further studies are required to assess the potential role of ERO1L as a biomarker for immunotherapy efficacy in LUAD.

scholarly journals Identification of potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma via integrated bioinformatics analysis

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052091001
Author(s):  
Ziqi Meng ◽  
Jiarui Wu ◽  
Xinkui Liu ◽  
Wei Zhou ◽  
Mengwei Ni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Interaction Network ◽  
Gene Expression Omnibus ◽  
Molecular Therapy ◽  
Integrated Analysis ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Interactive Analysis ◽  
Kaplan Meier

Objective The objective was to identify potential hub genes associated with the pathogenesis and prognosis of hepatocellular carcinoma (HCC). Methods Gene expression profile datasets were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HCC and normal samples were identified via an integrated analysis. A protein–protein interaction network was constructed and analyzed using the STRING database and Cytoscape software, and enrichment analyses were carried out through DAVID. Gene Expression Profiling Interactive Analysis and Kaplan–Meier plotter were used to determine expression and prognostic values of hub genes. Results We identified 11 hub genes ( CDK1, CCNB2, CDC20, CCNB1, TOP2A, CCNA2, MELK, PBK, TPX2, KIF20A, and AURKA) that might be closely related to the pathogenesis and prognosis of HCC. Enrichment analyses indicated that the DEGs were significantly enriched in metabolism-associated pathways, and hub genes and module 1 were highly associated with cell cycle pathway. Conclusions In this study, we identified key genes of HCC, which indicated directions for further research into diagnostic and prognostic biomarkers that could facilitate targeted molecular therapy for HCC.

scholarly journals Identification of Core Prognosis-Related Candidate Genes in Cervical Cancer via Integrated Bioinformatical Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-9 ◽  
Author(s):  
Jianxia Wei ◽  
Yang Wang ◽  
Kejian Shi ◽  
Ying Wang
Keyword(s):  
Gene Expression ◽  
Cervical Cancer ◽  
Protein Interactions ◽  
Gene Expression Omnibus ◽  
Venn Diagram ◽  
Protein Protein Interactions ◽  
Normal Tissues ◽  
Interactive Analysis ◽  
Kaplan Meier ◽  
Search Tool

Purposes. Cervical cancer (CC) is one of the highest frequently occurred malignant gynecological tumors with high rates of morbidity and mortality. Here, we aimed to identify significant genes associated with poor outcome. Materials and methods. Differentially expressed genes (DEGs) between CC tissues and normal cervical tissues were picked out by GEO2R tool and Venn diagram software. Database for Annotation, Visualization and Integrated Discovery (DAVID) was performed to analyze gene ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway. The protein-protein interactions (PPIs) of these DEGs were visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Afterwards, Kaplan-Meier analysis was applied to analyze the overall survival among these genes. The Gene Expression Profiling Interactive Analysis (GEPIA) was applied for further validation of the expression level of these genes. Results. The mRNA expression profile datasets of GSE63514, GSE27678, and GSE6791 were downloaded from the Gene Expression Omnibus database (GEO). In total, 76 CC tissues and 35 normal tissues were collected in the three profile datasets. There were totally 73 consistently expressed genes in the three datasets, including 65 up-regulated genes and 8 down-regulated genes. Of PPI network analyzed by Molecular Complex Detection (MCODE) plug-in, all 65 up-regulated genes and 4 down-regulated genes were selected. The results of the Kaplan-Meier survival analysis showed that 3 of the 65 up-regulated genes had a significantly worse prognosis, while 3 of the 4 down-regulated genes had a significantly better outcome. For validation in GEPIA, 4 of 6 genes (PLOD2, ANLN, AURKA, and AR) were confirmed to be significantly deregulated in CC tissues compared to normal tissues. Conclusion. We have identified three up-regulated (PLOD2, ANLN, and AURKA) and a down-regulated DEGs (AR) with poor prognosis in CC on the basis of integrated bioinformatical methods, which could be regarded as potential therapeutic targets for CC patients.

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