scholarly journals Comprehensive Analysis of Ferroptosis Regulators in Lung Adenocarcinomas Identifies Prognostic and Immunotherapy-Related Biomarkers

2021 ◽  
Vol 8 ◽  
Author(s):  
Sijin Sun ◽  
Wei Guo ◽  
Fang Lv ◽  
Guochao Zhang ◽  
Juhong Wang ◽  
...  
Keyword(s):  
Risk Score ◽  
Potential Role ◽  
Principal Component ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Mutation Burden ◽  
Related Risk ◽  
Lung Adenocarcinomas

Ferroptosis is a newly discovered type of programmed cell death that differs from canonical apoptosis. However, the potential role of ferroptosis in lung adenocarcinoma (LUAD) has not been elaborated. In total, 1,328 samples from databases and 36 ferroptosis regulators were included in this study. By combining random survival forest and principal component analysis algorithms, a robust prognostic ferroptosis-related risk score (FRRS) was constructed, and the performance was validated in three independent datasets. Based on the median risk score, two subgroups were identified. Then, comparisons, including of mutational profiles, functional enrichment analyses and immune components, were conducted between subgroups. An immunotherapy cohort was applied to explore potential therapeutic-related biomarkers. Finally, the clinical utility of FRRS was validated in a proteomic cohort. In the TCGA-LUAD cohort, FRRS was calculated using the expression of 11 selected genes, and patients with high FRRS had a significantly (p < 0.001) worse prognosis than those with low FRRS. Multivariate regression suggested that FRRS was an independent prognostic factor. Functional enrichment analysis indicated that FRRS was mainly involved in cell cycle, metabolic and immune-related pathways. Furthermore, FRRS was shown to be significantly (p < 0.001) associated with the abundance of CD8 T cells and tumor mutation burden (TMB). The combination of TMB and FANCD2 expression, the main contributor to FRRS, substantially increased the precision of predicting the therapeutic response. In conclusion, the present study revealed the potential role of ferroptosis regulators in LUAD and identified ferroptosis-related biomarkers for prognostic and immunotherapeutic predictions.

Construction of immune-related risk model for prognosis of hepatocellular carcinoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16683-e16683
Author(s):  
Yue Li ◽  
Ximing Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
High Risk ◽  
Risk Score ◽  
Risk Model ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Related Risk ◽  
Immune Related Genes

e16683 Background: Hepatocellular carcinoma is the most common malignant tumor. Although the treatment of HCC has significantly improved, the 5-year survival rate is still only 18%. There is increasing evidence that tumor immune microenvironment (TIM) plays critical roles during cancer initiation and progression. Based on the comprehensive exploration of the immunogenomic, an immune-related risk model was constructed to predict hepatocellular carcinoma prognosis. Methods: Transcriptomic data of HCC patients were downloaded from the TCGA database, and the differentially expressed immune-related genes (IRGs) (FDR < 0.01, |log2fold change| > 2) were identified. Functional enrichment analysis was performed to explore potential molecular mechanisms of the differentially expressed IRGs. By univariate and multivariate Cox regression analysis, we identified eight prognosis-related IRGs. Based on the expression levels of IRGs, we constructed the immune-related risk model. The Kaplan‐Meier (K‐M) survival curves, ROC curves, univariate and multivariate analysis were used to evaluate the immune-related risk model. According to the risk score, HCC patients were stratified into low and high-risk groups. CIBERSORT was applied to analyze the profiling difference of infiltrating immune cells between the two groups. Results: A total of 113 differentially expressed IRGs were identified, of which nine IRGs were correlated with the prognosis of HCC patients. Functional enrichment analysis showed that these genes were involved in immune response and immune signal pathway. The immune-related risk model consisted of eight IRGs (FABP6, RBP2, MAPT, BIRC5, PLXNA3, CSPG5, IL17D and STC2). The immune risk score was an independent prognostic factor (HR, 2.63 [1.93−3.58]; P = 8.16E−10) and the patients with a high-risk score tended to have a shorter OS than those with a low-risk score. In the TCGA cohort, high-risk patients tended to have an advanced stage. Moreover, we found that the patients in the high-risk group had higher fractions of T follicular cells helper and macrophages M0. The patients with low-risk scores had higher fractions of CD8+ T cells and CD4+ T cells. Conclusions: We have identified the immune-related risk model of hepatocellular carcinoma based on the expression profiles of eight immune-related genes. This model could predict prognosis and reflect the tumor immune microenvironment of HCC patients, which can provide new insights in the individualized treatment of HCC and potential novel targets for immunotherapy.

scholarly journals The Role of Circular RNA CDR1as/ciRS-7 in Regulating Tumor Microenvironment: A Pan-Cancer Analysis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 429 ◽  
Author(s):  
Zou ◽  
Zheng ◽  
Deng ◽  
Yang ◽  
Xie ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Circular Rna ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Receptor Interaction

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.

scholarly journals TET2/IDH1/2/WT1 and NPM1 Mutations Influence the RUNX1 Expression Correlations in Acute Myeloid Leukemia

Medicina ◽  
2020 ◽  
Vol 56 (12) ◽  
pp. 637
Author(s):  
Sergiu Pasca ◽  
Ancuta Jurj ◽  
Ciprian Tomuleasa ◽  
Mihnea Zdrenghea
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mutational Analysis ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Runx1 Expression ◽  
Acute Myeloid

Background and objectives: Mutational analysis has led to a better understanding of acute myeloid leukemia (AML) biology and to an improvement in clinical management. Some of the most important mutations that affect AML biology are represented by mutations in genes related to methylation, more specifically: TET2, IDH1, IDH2 and WT1. Because it has been shown in numerous studies that mutations in these genes lead to similar expression profiles and phenotypes in AML, we decided to assess if mutations in any of those genes interact with other genes important for AML. Materials and Methods: We downloaded the clinical data, mutational profile and expression profile from the TCGA LAML dataset via cBioPortal. Data were analyzed using classical statistical methods and functional enrichment analysis software represented by STRING and GOrilla. Results: The first step we took was to assess the 196 AML cases that had a mutational profile available and observe the mutations that overlapped with TET2/IDH1/2/WT1 mutations. We observed that RUNX1 mutations significantly overlap with TET2/IDH1/2/WT1 mutations. Because of this, we decided to further investigate the role of RUNX1 mutations in modulating the level of RUNX1 mRNA and observed that RUNX1 mutant cases presented higher levels of RUNX1 mRNA. Because there were only 16 cases of RUNX1 mutant samples and that mutations in this gene determined a change in mRNA expression, we further observed the correlation between RUNX1 and other mRNAs in subgroups regarding the presence of hypermethylating mutations and NPM1. Here, we observed that both TET2/IDH1/2/WT1 and NPM1 mutations increase the number of genes negatively correlated with RUNX1 and that these genes were significantly linked to myeloid activation. Conclusions: In the current study, we have shown that NPM1 and TET2/IDH1/2/WT1 mutations increase the number of negative correlations of RUNX1 with other transcripts involved in myeloid differentiation.

scholarly journals Transcriptomic Analysis Revealed an Emerging Role of Alternative Splicing in Embryonal Tumor with Multilayered Rosettes

Genes ◽  
2020 ◽  
Vol 11 (9) ◽  
pp. 1108
Author(s):  
Dina Hesham ◽  
Shahenda El-Naggar
Keyword(s):  
Cell Cycle ◽  
Alternative Splicing ◽  
Wnt Signaling Pathway ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Embryonal Tumor ◽  
Alternative Splicing Events ◽  
Regulation Of Cell Cycle

Embryonal tumor with multilayered rosettes (ETMR) is an aggressive and rare pediatric embryonal brain tumor. Amplification of C19MC microRNA cluster and expression of LIN28 are distinctive features of ETMR. Despite the increasing efforts to decipher ETMR, the biology remains poorly understood. To date, the role of aberrant alternative splicing in ETMR has not been thoroughly investigated. In the current study, a comprehensive analysis was performed on published unprocessed RNA-seq reads of tissue-matched ETMR and fetal controls datasets. Gene expression was quantified in samples using Kallisto/sleuth pipeline. For the alternative splicing analysis, STAR, SplAdder and rMATS were used. Functional enrichment analysis was subsequently performed using Metascape. The expression analysis identified a total of 3622 differentially expressed genes (DEGs) between ETMR and fetal controls while 1627 genes showed differential alternative splicing patterns. Interestingly, genes with significant alternative splicing events in ETMR were identified to be involved in signaling pathways such as ErbB, mTOR and MAPK pathways as well as ubiquitin-mediated proteolysis, cell cycle and autophagy. Moreover, up-regulated DEGs with alternative splicing events were involved in important biological processes including nuclear transport, regulation of cell cycle and regulation of Wnt signaling pathway. These findings highlight the role of aberrant alternative splicing in shaping the ETMR tumor landscape, and the identified pathways constitute potential therapeutic targets.

scholarly journals Identification and Validation of a Potential Prognostic 7-lncRNA Signature for Predicting Survival in Patients with Multiple Myeloma

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Yun Zhong ◽  
Zhe Liu ◽  
Dangchi Li ◽  
Qinyuan Liao ◽  
Jingao Li
Keyword(s):  
Gene Expression ◽  
Risk Score ◽  
Cox Regression ◽  
External Validation ◽  
Survival Rates ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Test Set ◽  
Cox Regression Analysis

Background. An increasing number of studies have indicated that the abnormal expression of certain long noncoding RNAs (lncRNAs) is linked to the overall survival (OS) of patients with myeloma. Methods. Gene expression data of myeloma patients were downloaded from the Gene Expression Omnibus (GEO) database (GSE4581 and GSE57317). Cox regression analysis, Kaplan-Meier, and receiver operating characteristic (ROC) analysis were performed to construct and validate the prediction model. Single sample gene set enrichment (ssGSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to predict the function of a specified lncRNA. Results. In this study, a seven-lncRNA signature was identified and used to construct a risk score system for myeloma prognosis. This system was used to stratify patients with different survival rates in the training set into high-risk and low-risk groups. Test set, the entire test set, the external validation set, and the myeloma subtype achieved the authentication of the results. In addition, functional enrichment analysis indicated that 7 prognostic lncRNAs may be involved in the tumorigenesis of myeloma through cancer-related pathways and biological processes. The results of the immune score showed that IF_I was negatively correlated with the risk score. Compared with the published gene signature, the 7-lncRNA model has a higher C-index (above 0.8). Conclusion. In summary, our data provide evidence that seven lncRNAs could be used as independent biomarkers to predict the prognosis of myeloma, which also indicated that these 7 lncRNAs may be involved in the progression of myeloma.

scholarly journals The Expression and Prognostic Role of Peroxiredoxins in Lung Cancer

2019 ◽  
Author(s):  
Ben Li ◽  
Bo Zhang ◽  
Qiong Wu ◽  
Xinming Chen ◽  
Xiang Cao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Expression Level ◽  
Normal Lung ◽  
Lung Cells ◽  
Analysis Tool

Background: Peroxiredoxins (Prxs) comprise antioxidant factors that are widely found in prokaryotes and eukaryotes. Abnormal expression of Prxs is closely related to tumorigenesis. Methods: This study examined the prognostic value and expression of Prxs in lung cancer by Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, Kaplan-Meier Plotter, cBioPortal and Functional Enrichment Analysis Tool (FunRich) databases. Results: We found that Prx1/2/3/4/5 were overexpressed in both lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) relative to normal lung cells. However, the expression level of Prx6 was lower in LUAD and higher in LUSC than normal lung cells. The level of Prx3 and Prx6 were associated with pathological stage. Prognostic analysis showed that elevated Prx1 and Prx2 expression were correlated with low Overall Survival (OS), whereas high Prx5 and Prx6 expression level predicted high OS. Conclusions: Our results effectively revealed the level of Prxs in lung cancer and its influence on the prognosis of lung carcinoma, contributing to the study of the role of Prxs in tumorigenesis.

scholarly journals Detecting Hub Genes Associated With Lauren Subtype of Gastric Cancer by Weighted Gene Co-Expression Network Analysis

2020 ◽  
Author(s):  
XU LIU ◽  
Li Yao ◽  
Jingkun Qu ◽  
Lin Liu ◽  
XU LIU ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Network Analysis ◽  
Cancer Survival ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Diffuse Gastric Cancer ◽  
Hub Genes ◽  
Gene Modules

Abstract Background Gastric cancer is a rather heterogeneous type of malignant tumor. Among the several classification system, Lauren classification can reflect biological and pathological differences of different gastric cancer.Method to provide systematic biological perspectives, we employ weighted gene co-expression network analysis to reveal transcriptomic characteristics of gastric cancer. GSE15459 and TCGA STAD dataset were downloaded. Co-expressional network was constructed and gene modules were identified. Result Two key modules blue and red were suggested to be associated with diffuse gastric cancer. Functional enrichment analysis of genes from the two modules was performed. Validating in TCGA STAD dataset, we propose 10 genes TNS1, PGM5, CPXM2, LIMS2, AOC3, CRYAB, ANGPTL1, BOC and TOP2A to be hub-genes for diffuse gastric cancer. Finally these ten genes were associated with gastric cancer survival. Conclusion More attention need to be paid and further experimental study is required to elucidate the role of these genes.

scholarly journals Altered Proteomic Profile of Adipose Tissue-Derived Mesenchymal Stem Cell Exosomes from Cats with Severe Chronic Gingivostomatitis

Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2466
Author(s):  
Antonio J. Villatoro ◽  
María del Carmen Martín-Astorga ◽  
Cristina Alcoholado ◽  
Casimiro Cárdenas ◽  
Fernando Fariñas ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Resolution Mass Spectrometry ◽  
Cell Communication ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Control Group ◽  
Proteomic Profile ◽  
Predisposing Factor

Feline chronic gingivostomatitis (FCGS) is a pathology with a complicated therapeutic approach and with a prevalence between 0.7 and 12%. Although the etiology of the disease is diverse, feline calicivirus infection is known to be a predisposing factor. To date, the available treatment helps in controlling the disease, but cannot always provide a cure, which leads to a high percentage of refractory animals. Mesenchymal stem cells (MSCs) play a pivotal role in the homeostasis and reparation of different tissues and have the ability to modulate the immune system responses. This ability is, in part, due to the capacity of exosomes to play a part in intercellular cell communication. However, the precise role of MSC-derived exosomes and their alterations in immunocompromised pathologies remains unknown, especially in veterinary patients. The goal of this work was to analyze the proteomic profile of feline adipose tissue-derived MSCs (fAd-MSCs) from calicivirus-positive FCGS patients, and to detect possible modifications of the exosomal cargo, to gain better knowledge of the disease’s etiopathogenesis. Using high-resolution mass spectrometry and functional enrichment analysis with Gene Ontology, exosomes isolated from the fAd-MSCs of five healthy cats and five calicivirus-positive FCGS patients, were pooled and compared. The results showed that the fAd-MSCs from cats suffering from FCGS not only had a higher exosome production, but also their exosomes showed significant alterations in their proteomic profile. Eight proteins were exclusively found in the exosomes from the FCGS group, and five proteins could only be found in the exosomes from the healthy cats. When comparing the exosomal cargo between the two groups, significant upregulation of 17 and downregulation of 13 proteins were detected in the FCGS group compared to the control group. These findings shed light on new perspectives on the roles of MSCs and their relation to this disease, which may help in identifying new therapeutic targets and selecting specific biomarkers.

scholarly journals Role of COL3A1 and POSTN on Pathologic Stages of Esophageal Cancer

2020 ◽  
Vol 19 ◽  
pp. 153303382097748
Author(s):  
Shao-wei Zhang ◽  
Nan Zhang ◽  
Na Wang
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Protein Protein Interaction ◽  
And Control ◽  
The Impact

Background: Esophageal cancer (EC) is a primary malignant tumor originating from the esophageal of the epithelium. Surgical resection is a potential treatment for EC, but this is only appropriate for patients who have locally resectable lesions suitable for surgery. However, most patients with EC are at a late stage when diagnosed. Therefore, there is an urgent need to further explore the pathogenesis of EC to enable early diagnosis and treatment. Methods: Our study downloaded 2 expression spectrum datasets (GSE92396 and GSE100942) in the Gene Expression Omnibus (GEO) database. GEO2 R was used to identify the Differentially expressed genes (DEGs) between the samples of EC and control. Using the DAVID tool to make the Functional enrichment analysis. Constructing A protein–protein interaction (PPI) network. Identifying the Hub genes. The impact of hub gene expression on overall survival and their expression based on immunohistochemistry were analyzed. Associated microRNAs were also predicted. Results: There were 36 common DEGs identified. The analysis of GO and KEGG results shown that the variations were predominantly concentrated in the extracellular matrix (ECM), ECM organization, DNA binding, platelet activation, and ECM-receptor interactions. COL3A1 and POSTN had high expression in EC tissues which was compared with their expression in healthy tissues. Analysis of pathologic stages showed that when COL3A1 and POSTN were highly expressed, the stage of the pathologic of EC patients was relatively high (P < 0.005). Conclusions: COL3A1 and POSTN may play an important role in the advancement and occurrence of EC. These genes could provide some novel ideas and basis for the diagnosis and targeted treatment of EC.

scholarly journals Meta-Analysis of miRNAs and Their Involvement as Biomarkers in Oral Cancers

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Andleeb Zahra ◽  
Itrat Rubab ◽  
Sumaira Malik ◽  
Amina Khan ◽  
Muhammad Jawad Khan ◽  
...  
Keyword(s):  
Diagnostic Marker ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Oral Carcinoma ◽  
Functional Enrichment ◽  
Oral Cancers ◽  
Extracellular Mirnas ◽  
Potential Use

Oral Squamous Cell Carcinoma (OSCC) is one of the most common cancers worldwide. Recent studies have highlighted the role of miRNA in disease pathology, indicating its potential use as an early diagnostic marker. Dysregulated expression of miRNAs is known to affect cell growth, and these may function as tumor suppressors or oncogenes in various cancers. The main objective of this study was to characterize the extracellular miRNAs involved in oral cancer (OC) that can potentially be used as biomarkers of OC. A total of 318 miRNAs involved in oral carcinoma were shortlisted. Differentially expressed genes (DEGs) of oral carcinoma from reported experiments were identified. Common genes between lists of DEGs of OC of each miRNA were identified. These common genes are the targets of specific miRNA, which may be used as biomarkers of OC. A list of significant biomarkers for cancer was generated like CDH2 and CDK7, and functional enrichment analysis identified the role of miRNAs in major pathways like cell adhesion molecules pathway affected by cancer. We observed that at least 25 genes like ABCF3, ALDH2, CD163L1, and so forth are regulated by a maximum number of miRNAs; thereby, they can be used as biomarkers of OC.

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