scholarly journals TAL1-mediated epigenetic modifications down-regulate the expression of GIMAP family in non-small cell lung cancer

2019 ◽  
Author(s):  
Zhongxiang Tang ◽  
Lili Wang ◽  
Pei Dai ◽  
Pinglang Ruan ◽  
Dan Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epigenetic Modification ◽  
Lung Squamous Cell Carcinoma ◽  
Epigenetic Modifications ◽  
Small Cell ◽  
The Cancer Genome Atlas ◽  
Biological Databases ◽  
Small Cell Lung

AbstractBackgroudThe study was designed to explore the role of GIMAP family in non-small cell lung cancer (NSCLC) and its possible expression regulation mechanisms using existing biological databases including encyclopedia of DNA elements (ENCODE), gene expression omnibus (GEO), and the cancer genome atlas (TCGA).MethodsLung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) were used to evaluate the expression of GIMAPs in TCGA. Five NSCLC datasets were then selected from GEO for validation. RNA-seq and Chip-seq data from ENCODE and GEO were used to observe epigenetic modifications on the chromosomes of GIAMPs in NSCLC. We constructed protein-protein interaction (PPI) network to reveal the main interacting proteins of GIMAPs. We then analyzed the correlation and regulatory mechanism between TAL1 and the expression of GIMAP family. We also used Kaplan-Meier for survival analysis.ResultsAll 7 genes in the GIMAP family were down-regulated in NSCLC. H3K4me3 and H3K27ac disappeared, while H3K27me3 increased on the chromosome of this family. The expression of TAL1 was positively correlated with the expression of GIMAPs. sh-TAL1 significantly down-regulated the expression of GIMAP family through epigenetic modification. High expression of GIMAPs and TAL1 was found to be associated with a good prognosis of NLCSC.ConclusionThe downregulation of TAL1 caused the disappearance of H3K27ac and H3K4me3. It also caused an increase in H3K27me3 on the GIMAPs gene, eventually leading to the overall downregulation of the GIMAP family genes.

scholarly journals Identification of Prognostic miRNAs Associated With Immune Cell Tumor Infiltration Predictive of Clinical Outcomes in Patients With Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yuepeng Zhang ◽  
Kai Mi ◽  
Zhiheng Li ◽  
Lixia Qiang ◽  
Meiyu Lv ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Mirna Target ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
The Cancer Genome Atlas ◽  
Mirna Signature ◽  
Small Cell Lung ◽  
Clinical Prognosis

BackgroundA detailed means of prognostic stratification in patients with non-small cell lung cancer (NSCLC) is urgently needed to support individualized treatment plans. Recently, microRNAs (miRNAs) have been used as biomarkers due to their previously reported prognostic roles in cancer. This study aimed to construct an immune-related miRNA signature that effectively predicts NSCLC patient prognosis.MethodsThe miRNAs and mRNA expression and mutation data of NSCLC was obtained from The Cancer Genome Atlas (TCGA). Immune-associated miRNAs were identified using immune scores calculated by the ESTIMATE algorithm. LASSO-penalized multivariate survival models were using for development of a tumor immune-related miRNA signature (TIM-Sig), which was evaluated in several public cohorts from the Gene Expression Omnibus (GEO) and the CellMiner database. The miRTarBase was used for constructing the miRNA-target interactions.ResultsThe TIM-Sig, including 10 immune-related miRNAs, was constructed and successfully predicted overall survival (OS) in the validation cohorts. TIM-Sig score negatively correlated with CD8+ T cell infiltration, IFN-γ expression, CYT activity, and tumor mutation burden. The correlation between TIM-Sig score and genomic mutation and cancer chemotherapeutics was also evaluated. A miRNA-target network of 10 miRNAs in TIM-Sig was constructed. Further analysis revealed that these target genes showed prognostic value in both lung squamous cell carcinoma and adenocarcinoma.ConclusionsWe concluded that the immune-related miRNAs demonstrated a potential value in clinical prognosis.

Regulation of EP receptors in non-small cell lung cancer by epigenetic modifications

2009 ◽  
Vol 45 (17) ◽  
pp. 3087-3097 ◽  
Author(s):  
Steven G. Gray ◽  
Nael Al-Sarraf ◽  
Anne-Marie Baird ◽  
Mary-Clare Cathcart ◽  
Eilish McGovern ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epigenetic Modifications ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ep Receptors

scholarly journals Co-expression Network and Prognosis Analyses of Pyroptosis-related Genes in Non-small Cell Lung Cancer

2021 ◽  
Author(s):  
Zixiao Liu ◽  
Xudong Liu ◽  
Yu Zhang ◽  
Yongjie Zhou ◽  
Shuaibin Lian ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Hydrophobic Interactions ◽  
Tumor Staging ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
Differentially Expressed ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract Lung cancer is very difficult to diagnose in the its early stages because of its initial asymptomatic characteristics. In recent years, pyrolysis has been shown identified as a novel type of programmed cell death with inflammation mediated by the gasdermin family. In this study, 33 differentially-expressed pyroptosis-related genes were commonly identified in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. Tumor-related gasdermin family genes that were significantly differentially expressed in non-small cell lung cancer (NSCLC) tissues were identified by our co-expression network analysis. Among them, the mRNA level of GSDMB gene had significant impacts on tumor staging and survival rates of NSCLC patients. Therefore, this gene is a potential new therapeutic target for the treatment of NSCLC. In addition, the high expression levels of GSDMC/D were significantly correlated with the low overall survival (OS), progression-free survival (FP) and post-progression survival (PPS) of NSCLC patients. Therefore, this gene is a potential oncogene for NSCLC. Furthermore, four small molecules (erastin, cefotiam, metanephrine, and vorinostat) that could most significantly reverse the NSCLC gene expression were identified. They interacted with GSDMB proteins mainly through H-bonds and hydrophobic interactions. This study provides new therapeutic targets and prognostic makers for NSCLC patients.

scholarly journals Epigenetic modifications of the VGF gene in human non-small cell lung cancer tissues pave the way towards enhanced expression

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Sebastian Marwitz ◽  
Lena Heinbockel ◽  
Swetlana Scheufele ◽  
Dörte Nitschkowski ◽  
Christian Kugler ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Epigenetic Modifications ◽  
Small Cell ◽  
Small Cell Lung ◽  
Enhanced Expression ◽  
Cancer Tissues ◽  
The Way

RORγ agonist LYC-55716, a novel small molecule immunotherapy: Rationale for clinical evaluation in non-small cell lung cancer based on translational and bioinformatic evaluation.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 171-171
Author(s):  
Laura Carter ◽  
Xikui Liu ◽  
Hongxiu Li ◽  
Elizabeth Zawidzka ◽  
Yilin Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cell Formation ◽  
Small Cell ◽  
The Cancer Genome Atlas ◽  
Orphan Receptor ◽  
Small Cell Lung

171 Background: Retinoic acid receptor–related orphan receptor γ (RORγ) agonists modulate immune cell gene expression to enhance effector function and decrease regulatory T cell formation and expression of checkpoint pathways. RORγ agonists have demonstrated antitumor activity in syngeneic tumor models. Translational and bioinformatic assessments were conducted to support inclusion of patients with non–small-cell lung cancer (NSCLC) in a Phase 2a expansion of clinical trial LYC-55716-1001 (NCT02929862). Methods: The Cancer Genome Atlas (TCGA) NSCLC dataset was evaluated for (a) expression of RORγ and RORγ-inducing cytokines and correlation with survival; (b) genes related to RORγ biology, biomarkers of endogenous RORγ agonists; and (c) tumor microenvironment (TME) immune profiles. RORγ expression and the in vitro effects of a RORγ agonist on peripheral blood mononuclear cells (PBMCs) from lung adenocarcinoma (LA) and squamous cell carcinoma (SCC) patients were assessed. Results: In TCGA, 25% of NSCLC tumors expressed moderate/high levels of RORγ, suggesting infiltration of Type 17 cells. There was a statistically significant correlation between high RORγ expression and improved survival in LA patients. Genes that support Type 17 cell formation (IL1B, IL23A, IL6) were expressed in ~50% of tumors. RORγ expression was confirmed in PBMCs isolated from LA and SCC patients. Analysis of TCGA data and patient samples identified low expression of sterol efflux and uptake genes, suggesting low levels of endogenous RORγ agonist in TME. In TCGA, high mutational burden and high expression of immune-related genes were found in NSCLC tumors. RORγ agonist treatment of PBMCs from LA and SCC patients increased IL-17A and IL-26 (LA and SCC) and decreased PD1 (LA). In Phase 1 clinical testing, LYC-55716 has been well tolerated, demonstrating long-term disease stabilization in heavily pretreated patients. Conclusions: Bioinformatic analyses of RORγ expression/biology, correlation with improved survival, plus in vitro findings support inclusion of NSCLC in an ongoing Phase 2 clinical trial of LYC-55716.

scholarly journals Expression, Prognosis and Gene Regulation Network of NFAT Transcription Factors in Non-Small Cell Lung Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Jin Ma ◽  
Rao Du ◽  
Yan Huang ◽  
Wen Zhong ◽  
Huan Gui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Mrna Expression ◽  
Cell Lung Cancer ◽  
Expression Patterns ◽  
Lung Squamous Cell Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Aberrant Expression ◽  
Expression Levels

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The nuclear factor of activated T cells (NFAT) family is implicated in tumorigenesis and progression in various types of cancer. However, little is known about their expression patterns, distinct prognostic values, and potential regulatory networks in NSCLC. In this study, we comprehensively analyzed the distinct expression and prognostic value of NFATs in NSCLC through various large databases, including the Oncomine, UCSC Xena Browser, UALCAN databases, Kaplan–Meier Plotter, cBioPortal, and Enrichr. In lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), NFAT1/2/4/5 mRNA expression levels were significantly decreased and NFAT3 mRNA expression level was significantly increased. The cBioPortal database analysis showed that the mRNA dysregulation was one of the single most important factors for NFAT alteration in LUAD and LUSC and that both LUAD and LUSC cases with the alterations in the mRNA expression of NFATs had significantly better overall survival (OS). High expression levels of NFAT1/2/4/5 were significantly associated with better OS in LUAD, whereas high NFAT3 expression led to a worse OS. Overexpression of NFAT1/2 predicted better OS in LUSC, whereas high NFAT5 expression led to a worse OS. The networks for NFATs and the 50 most frequently altered neighbor genes in LUAD and LUSC were also constructed. NFATs and genes significantly associated with NFAT mRNA expression in LUAD and LUSC were significantly enriched in the cGMP-dependent protein kinase and Wnt signaling pathways. These results showed that the NFAT family members displayed varying degrees of abnormal expressions, suggesting that NFATs may be therapeutic targets for patients with NSCLC. Aberrant expression of NFATs was found to be associated with OS in the patients with NSCLC; among NFATs, NFAT3/4 may be new biomarkers for the prognosis of LUAD. However, further studies are required to validate our findings.

scholarly journals A Multi-Omics Network of a Seven-Gene Prognostic Signature for Non-Small Cell Lung Cancer

2021 ◽  
Vol 23 (1) ◽  
pp. 219
Author(s):  
Qing Ye ◽  
Brianne Falatovich ◽  
Salvi Singh ◽  
Alexey V. Ivanov ◽  
Timothy D. Eubank ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Transcriptional Regulatory Network ◽  
Early Stage ◽  
Recurrence Risk ◽  
Small Cell ◽  
The Cancer Genome Atlas ◽  
Small Cell Lung ◽  
Western Blots

There is an unmet clinical need to identify patients with early-stage non-small cell lung cancer (NSCLC) who are likely to develop recurrence and to predict their therapeutic responses. Our previous study developed a qRT-PCR-based seven-gene microfluidic assay to predict the recurrence risk and the clinical benefits of chemotherapy. This study showed it was feasible to apply this seven-gene panel in RNA sequencing profiles of The Cancer Genome Atlas (TCGA) NSCLC patients (n = 923) in randomly partitioned feasibility-training and validation sets (p < 0.05, Kaplan–Meier analysis). Using Boolean implication networks, DNA copy number variation-mediated transcriptional regulatory network of the seven-gene signature was identified in multiple NSCLC cohorts (n = 371). The multi-omics network genes, including PD-L1, were significantly correlated with immune infiltration and drug response to 10 commonly used drugs for treating NSCLC. ZNF71 protein expression was positively correlated with epithelial markers and was negatively correlated with mesenchymal markers in NSCLC cell lines in Western blots. PI3K was identified as a relevant pathway of proliferation networks involving ZNF71 and its isoforms formulated with CRISPR-Cas9 and RNA interference (RNAi) profiles. Based on the gene expression of the multi-omics network, repositioning drugs were identified for NSCLC treatment.

Sign in / Sign up

Export Citation Format

Share Document