Dataset Information

CFHR1 is a potentially downregulated gene in lung adenocarcinoma.

ABSTRACT: There is increasing evidence that human complement factor H?related protein 1 (CFHR1) plays a crucial role in the development of malignant diseases. However, few studies have identified the roles of CFHR1 in the occurrence and prognosis of lung adenocarcinoma (LADC). In the present study, comprehensive bioinformatic analyses of data obtained from the Oncomine platform, UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that CFHR1 expression is significantly reduced in both LADC tissues and cancer cells. The patients presenting with downregulation of CFHR1 had significantly lower overall survival (OS) and post progression survival (PPS) times. Through analysis of the datasets from Gene Expression Omnibus database, we found that the compound actinomycin D promoted CFHR1 expression, further displaying the cytotoxic effect in the LADC cell line A549. In addition, the expression level of CFHR1 in the cisplatin?resistant LADC cell line CDDP?R (derived from H460) was also significantly reduced. Our research demonstrated that low levels of CFHR1 are specifically found in LADC samples, and CFHR1 could serve as a potential therapeutic target for this subset of lung cancers. Determination of the detailed roles of CFHR1 in LADC biology could provide insightful information for further investigations.

SUBMITTER: Wu G

PROVIDER: S-EPMC6755197 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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CFHR1 is a potentially downregulated gene in lung adenocarcinoma.

Wu Geting G Yan Yuanliang Y Wang Xiang X Ren Xinxin X Chen Xi X Zeng Shuangshuang S Wei Jie J Qian Long L Yang Xue X Ou Chunlin C Lin Wei W Gong Zhicheng Z Zhou Jianhua J Xu Zhijie Z

Molecular medicine reports 20190903 4

There is increasing evidence that human complement factor H‑related protein 1 (CFHR1) plays a crucial role in the development of malignant diseases. However, few studies have identified the roles of CFHR1 in the occurrence and prognosis of lung adenocarcinoma (LADC). In the present study, comprehensive bioinformatic analyses of data obtained from the Oncomine platform, UALCAN and Gene Expression Profiling Interactive Analysis (GEPIA) demonstrated that CFHR1 expression is significantly reduced in ...[more]

PMID: 31485643

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Project description:PurposeAbnormal CLEC9A expression is concerned with carcinogenesis. However, the role of CLEC9A in lung adenocarcinoma (LUAD) remains unknown. The goal of this study was to reveal the role of CLEC9A in LUAD based on bioinformatics and cellular functional experiments.Materials and methodsData available from The Cancer Genome Atlas (TCGA) were employed to study CLEC9A expression and mutations in LUAD. Expression and alterations of CLEC9A were analyzed using UALCAN and cBioPortal, respectively. Kaplan-Meier analysis was used to analyze the effect of CLEC9A on the survival of LUAD. Protein-protein interaction (PPI) network was built using GeneMANIA analysis. The similar genes of CLEC9A were obtained using GEPIA analysis, while co-expression genes correlated with CLEC9A were identified using LinkedOmics analysis. The effects of CLEC9A expression on immune cell infiltration was assessed. The effect of CLEC9A on the proliferation, apoptosis, cell cycle distribution, and invasion of human LUAD cells was detected in the LUAD cell line.ResultsCLEC9A was downregulated and the CLEC9A gene was often altered in LUAD. The survival of LUAD patients was correlated with the expression level of CLEC9A. The similar genes of CLEC9A were linked to functional networks involving positive regulation of interleukin-12 production, plasma membrane and CD40 receptor binding, primary immunodeficiency, intestinal immune network for IgA production, and cell adhesion molecules pathways. Cell cycle, apoptosis, EMT, and RAS/MAPK were significantly enriched pathways in positive and negative correlation genes with CLEC9A. A difference in the immune infiltration level of immune cell between the high and low CLEC9A expression groups was observed. Somatic cell copy number alternations (CNAs) of the CLEC9A, including arm-level gain and arm-level deletion, observably changed the infiltration levels of B cells, CD4+ T cells, macrophages, and neutrophils in LUAD. Except for LAG3, the expression of CD274, CTLA4, PDCD1, and TIGIT was positively correlated with the expression level of CLEC9A. After transfection, overexpression and knockdown of CLEC9A could affect the proliferation, apoptosis, cell cycle distribution, and invasion of LUAD cells.ConclusionCLEC9A is associated with prognosis and tumor immune microenvironment of LUAD, suggesting that CLEC9A may be considered as a novel biomarker for LUAD.

Project description:BackgroundLung adenocarcinoma (LUAD) is a common lung cancer with a high mortality, for which microRNAs (miRNAs) play a vital role in its regulation. Multiple messenger RNAs (mRNAs) may be regulated by miRNAs, involved in LUAD tumorigenesis and progression. However, the miRNA-mRNA regulatory network involved in LUAD has not been fully elucidated.MethodsDifferentially expressed miRNAs and mRNA were derived from the Cancer Genome Atlas (TCGA) dataset in tissue samples and from our microarray data in plasma (GSE151963). Then, common differentially expressed (Co-DE) miRNAs were obtained through intersected analyses between the above two datasets. An overlap was applied to confirm the Co-DEmRNAs identified both in targeted mRNAs and DEmRNAs in TCGA. A miRNA-mRNA regulatory network was constructed using Cytoscape. The top five miRNA were identified as hub miRNA by degrees in the network. The functions and signaling pathways associated with the hub miRNA-targeted genes were revealed through Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The key mRNAs in the protein-protein interaction (PPI) network were identified using the STRING database and CytoHubba. Survival analyses were performed using Gene Expression Profiling Interactive Analysis (GEPIA).ResultsThe miRNA-mRNA regulatory network consists of 19 Co-DEmiRNAs and 760 Co-DEmRNAs. The five miRNAs (miR-539-5p, miR-656-3p, miR-2110, let-7b-5p, and miR-92b-3p) in the network were identified as hub miRNAs by degrees (>100). The 677 Co-DEmRNAs were targeted mRNAs from the five hub miRNAs, showing the roles in the functional analyses of the GO analysis and KEGG pathways (inclusion criteria: 836 and 48, respectively). The PPI network and Cytoscape analyses revealed that the top ten key mRNAs were NOTCH1, MMP2, IGF1, KDR, SPP1, FLT1, HGF, TEK, ANGPT1, and PDGFB. SPP1 and HGF emerged as hub genes through survival analysis. A high SPP1 expression indicated a poor survival, whereas HGF positively associated with survival outcomes in LUAD.ConclusionThis study investigated a miRNA-mRNA regulatory network associated with LUAD, exploring the hub miRNAs and potential functions of mRNA in the network. These findings contribute to identify new prognostic markers and therapeutic targets for LUAD patients in clinical settings.

Project description:Backgrounds Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, which is the leading cause of cancer death. Dysregulation of cell proliferation and death plays a crucial role in the development of LUAD. As of recently, the role of a new form of cell death, cuproptosis, and it has attracted more and more attention. As of yet, it is not clear whether cuproptosis is involved in the progression of LUAD. Methods An integrated set of bioinformatics tools was utilized to analyze the expression and prognostic significance of cuproptosis-related genes. Meanwhile, a robust risk signature was developed using machine learning based on prognostic cuproptosis-related genes and explored the value of prognostic cuproptosis-related signature for clinical applications, functional enrichment and immune landscape. Lastly, the dysregulation of the cuproptosis-related genes in LUAD was validated by in vitro experiment. Results In this study, first, cuproptosis-related genes were found to be differentially expressed in LUAD patients of public databases, and nine of them had prognostic value. Next, a cuproptosis-related model with five features (DLTA, MTF1, GLS, PDHB and PDHA1) was constructed to separate the patients into high- and low-risk groups based on median risk score. Internal validation set and external validation set were used for model validation and evaluation. What’s more, Enrichment analysis of differential genes and the WGCNA identified that cuproptosis-related signatures affected tumor prognosis by influencing tumor immunity. Small molecule compounds were predicted based on differential expressed genes to improve poor prognosis in the high-risk group and a nomogram was constructed to further advance clinical applications. In closing, our data showed that FDX1 affected the prognosis of lung cancer by altering the expression of cuproptosis-related signature. Conclusion A new cuproptosis-related signature for survival prediction was constructed and validated by machine learning algorithm and in vitro experiments to reflect tumor immune infiltration in LUAD patients. The purpose of this article was to provide a potential diagnostic and therapeutic strategy for LUAD.

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CFHR1 is a potentially downregulated gene in lung adenocarcinoma.

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CFHR1 is a potentially downregulated gene in lung adenocarcinoma.

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