scholarly journals A mRNA-miRNA-lncRNA regulatory network related to potential pathogenesis and prognostic markers of Non- small cell lung cancer

2021 ◽  
Author(s):  
Fei Wang ◽  
Chong Yuan ◽  
Yanfang Yang ◽  
Bo Liu ◽  
Hezhen Wu
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Malignant Tumors ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Hub Genes ◽  
Incidence And Mortality ◽  
Nsclc Patients

Abstract Non-small cell lung cancer (NSCLC) is one of the most malignant tumors with the fastest increasing incidence and mortality rate, but the etiology of NSCLC is still not clear. Most of lncRNAs have some structural similarities with mRNAs, suggesting that miRNAs negatively regulate the expression of lncRNAs to affect the occurrence and development of tumor. Therefore, system bioinformatics was used to explore the potential biomarkers and possible pathogenesis of NSCLC in this study. Firstly, all the clinical information and transcriptome data were downloaded from GEO and TCGA databases. R language was used to analyze the differentially expressed genes (DEGs) in NSCLC and normal lung tissues. Then, 50 overlapped DEGs were obtained via Venn database, including 10 down-regulated mRNAs and 40 down-regulated mRNAs. Secondly, the top 20 DEGs were selected for KEGG pathway and GO enrichment analysis. After screening 4 HUB genes related to the survival and prognosis of NSCLC patients, their prognosis models were established. Meanwhile, HUB genes related miRNAs and lncRNAs were screened. Finally, a mRNA-miRNA-lncRNA network related to the survival and prognosis of NSCLC patients was established, including 4 up-regulated mRNAs, 3 up-regulated miRNAs, 10 down-regulated miRNAs, 6 up-regulated lncRNAs and 19 down-regulated lncRNAs. Subject terms: Non-small cell lung cancer, mRNA-miRNA-lncRNA, pathogenesis, prognostic biomarkers.

scholarly journals Prognostic significance of CD276 in non-small cell lung cancer

Open Medicine ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. 805-812
Author(s):  
Changgong Zhang ◽  
Xuezhi Hao
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Expression Level ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Nsclc Tissue ◽  
Normal Tissues ◽  
Nsclc Patients

AbstractBackgroundThe expression and significance of CD276 in non-small cell lung cancer (NSCLC) was explored.MethodThe BioGPS database was used to analyze the expression level of CD276 in normal tissues. Studies on the expression of CD276 in NSCLC patients using the Oncomine database. The prognostic roles of CD276 in NSCLC was studied using the Kaplan-Meier plotter database.ResultThe BioGPS database showed CD276 expression in all the human normal tissues. Compared with normal lung tissue, CD276 gene highly expressed in NSCLC tissue at mRNA level (P<0.05). The expression level of CD276 gene was negatively correlated with overall survival (OS) of NSCLC patients. Subgroup analysis showed that CD276 expression level had a significant effect on OS of patients with lung adenocarcinoma, while in squamous cell carcinoma its expression level had no significant effect on OS.ConclusionAccording to the information mined from the tumor gene database, CD276 mRNA was found highly expressed in NSCLC tissue and the expression of CD276 has a significant impact on survival of NSCLC patients, which provides an important theoretical basis for further study of the role of CD276 in the occurrence and development of NSCLC.

scholarly journals Expression of long noncoding RNA NBAT1 is associated with the outcome of patients with non-small cell lung cancer

2020 ◽  
Vol 66 (7) ◽  
pp. 898-903
Author(s):  
Da-Ling Wang ◽  
Peng Yuan ◽  
Ji-Yuan Tian
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Prognostic Significance ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Nsclc Patients

SUMMARY OBJECTIVE Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) has been reported to be involved in cancer progression. However, the clinical significance of NBAT1 in non-small cell lung cancer (NSCLC) is still unclear. Our present research aimed to explore whether NBAT1 serves as a biomarker for NSCLC prognosis. METHODS The expression of NBAT1 was examined by RT-PCR in tissue samples of 162 NSCLC patients and was compared with the adjacent non-tumor lung specimens. Then the association between NBAT1 expression and clinical-pathological parameters was further evaluated. Survival analysis was performed using the Kaplan-Meier method. The prognostic significance of NBAT1 expression in NSCLC patients was explored by the use of univariate and multivariate analyses. RESULTS NBAT1 expression was prominently decreased in NSCLC tissues compared with matched normal lung specimens (p < 0.01). Moreover, survival analyses indicated that patients with low expression displayed dramatically decreased 5-year overall survival (p = 0.008). CONCLUSIONS NBAT1 expression might contribute to tumor progression and poor prognosis of NSCLC and might be a new therapeutic target in NSCLC.

α,1,6-Fucosyltransferase (FUT8) regulates cancer-promoting capacities of cancer-associated fibroblasts (CAFs) through the modification of EGFR core fucosylation in non-small cell lung cancer

2019 ◽  
Author(s):  
Fengzhou Li ◽  
Shilei Zhao ◽  
Yanwei Cui ◽  
Jiaqi Qiang ◽  
Tao Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Cancer Associated Fibroblasts ◽  
Small Cell Lung ◽  
Nsclc Patients

Abstract BackgroundCancer-associated fibroblasts (CAFs), the main component of the tumor microenvironment (TME) of NSCLC, are activated by phenotypic transformation into myofibroblasts. α,1,6-fucosyltransferase (FUT8), the key enzyme catalyzing core α,1,6-fucosylation (CF), plays important roles in multiple malignancies. In the current study, we investigated the functions and mechanism of CF mediated by FUT8 in CAFs in NSCLC through bioinformatics analysis, retrospective clinical studies and in vitro/in vivo laboratory experiments.MethodsBioinformatics was used to reveal the relationship between FUT8 and CAFs. Resected specimens, clinical data and prognostic information from 135 NSCLC patients were analyzed to assess the prognostic value of FUT8 in CAFs. Primary CAFs and normal lung fibroblasts were extracted from NSCLC patients and cocultured with NSCLC cell lines in a novel noncontact coculture device produced by 3D printing. In vivo, CAF/NSCLC coinjection tumorigenesis assay was performed in nude mice to study the function of FUT8/CF in TME. The mechanisms of FUT8/CF in CAFs regulating the cocultured NSCLC cells were investigated in cell and molecular experiments. ResultsFUT8 in CAFs is an independent risk factor for prognosis. FUT8/CF in CAFs is essential for CAFs to maintain their ability to promote NSCLC. FUT8/CF in CAFs is responsible for the cancer-promoting capacities of CAFs and lead to a malignant tumor microenvironment. CF modification enhances tyrosine phosphorylation of EGFR in CAFs, which causes activation of downstream signalings of EGFR and maintains cancer-promoting properties of CAFs.ConclusionFUT8 regulates cancer-promoting capacities of CAFs via the modification of EGFR CF in non-small cell lung cancer.

Comprehensive analysis of non-small-cell lung cancer microarray datasets identifies several prognostic biomarkers

2019 ◽  
Vol 15 (27) ◽  
pp. 3135-3148
Author(s):  
Xiuxiu Qin ◽  
Ruoshi Chen ◽  
Rui Xiong ◽  
Zimiao Tan ◽  
Shanshan Gao ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Gene Expression Omnibus ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hub Genes ◽  
Protein Protein Interaction ◽  
Nsclc Patients ◽  
Microarray Datasets

Aim: To find accurate and effective biomarkers for diagnosis of non-small-cell lung cancer (NSCLC) patients. Materials & methods: We downloaded microarray datasets GSE19188, GSE33532, GSE101929 and GSE102286 from the database of Gene Expression Omnibus. We screened out differentially expressed genes (DEGs) and miRNAs (DEMs) with GEO2R. We also performed analyses for the enrichment of DEGs’ and DEMs’ function and pathway by several tools including database for annotation, visualization and integrated discovery, protein–protein interaction and Kaplan–Meier-plotter. Results: Total 913 DEGs were screened out, among which ten hub genes were discovered. All the hub genes were linked to the worsening overall survival of the NSCLC patients. Besides, 98 DEMs were screened out. MiR-9 and miR-520e were the most significantly regulated miRNAs. Conclusion: Our results could provide potential targets for the diagnosis and treatment of NSCLC.

scholarly journals Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA)

Cancers ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 37 ◽  
Author(s):  
Magdalena Niemira ◽  
Francois Collin ◽  
Anna Szalkowska ◽  
Agnieszka Bielska ◽  
Karolina Chwialkowska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Network Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Molecular Signature ◽  
Normal Lung ◽  
Specific Gene ◽  
Small Cell Lung ◽  
Hub Genes

Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies consisting essentially of adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although the diagnosis and treatment of ADC and SCC have been greatly improved in recent decades, there is still an urgent need to identify accurate transcriptome profile associated with the histological subtypes of NSCLC. The present study aims to identify the key dysregulated pathways and genes involved in the development of lung ADC and SCC and to relate them with the clinical traits. The transcriptional changes between tumour and normal lung tissues were investigated by RNA-seq. Gene ontology (GO), canonical pathways analysis with the prediction of upstream regulators, and weighted gene co-expression network analysis (WGCNA) to identify co-expressed modules and hub genes were used to explore the biological functions of the identified dysregulated genes. It was indicated that specific gene signatures differed significantly between ADC and SCC related to the distinct pathways. Of identified modules, four and two modules were the most related to clinical features in ADC and SCC, respectively. CTLA4, MZB1, NIP7, and BUB1B in ADC, as well as GNG11 and CCNB2 in SCC, are novel top hub genes in modules associated with tumour size, SUVmax, and recurrence-free survival. Our research provides a more effective understanding of the importance of biological pathways and the relationships between major genes in NSCLC in the perspective of searching for new molecular targets.

scholarly journals Genetic Variants of CLPP and M1AP Are Associated With Risk of Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xianghan Li ◽  
Yiran Zou ◽  
Teng Li ◽  
Thomas K. F. Wong ◽  
Ryan T. Bushey ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Patients ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Advanced Stage ◽  
Small Cell Lung ◽  
Lung Cancer Patients ◽  
Nsclc Patients

BackgroundSingle nucleotide polymorphisms (SNPs) are often associated with distinct phenotypes in cancer. The present study investigated associations of cancer risk and outcomes with SNPs discovered by whole exome sequencing of normal lung tissue DNA of 15 non-small cell lung cancer (NSCLC) patients, 10 early stage and 5 advanced stage.MethodsDNA extracted from normal lung tissue of the 15 NSCLC patients was subjected to whole genome amplification and sequencing and analyzed for the occurrence of SNPs. The association of SNPs with the risk of lung cancer and survival was surveyed using the OncoArray study dataset of 85,716 patients (29,266 cases and 56,450 cancer-free controls) and the Prostate, Lung, Colorectal and Ovarian study subset of 1,175 lung cancer patients.ResultsWe identified 4 SNPs exclusive to the 5 patients with advanced stage NSCLC: rs10420388 and rs10418574 in the CLPP gene, and rs11126435 and rs2021725 in the M1AP gene. The variant alleles G of SNP rs10420388 and A of SNP rs10418574 in the CLPP gene were associated with increased risk of squamous cell carcinoma (OR = 1.07 and 1.07; P = 0.013 and 0.016, respectively). The variant allele T of SNP rs11126435 in the M1AP gene was associated with decreased risk of adenocarcinoma (OR = 0.95; P = 0.027). There was no significant association of these SNPs with the overall survival of lung cancer patients (P &gt; 0.05).ConclusionsSNPs identified in the CLPP and M1AP genes may be useful in risk prediction models for lung cancer. The previously established association of the CLPP gene with cancer progression lends relevance to our findings.

scholarly journals Identification of potential target genes and crucial pathways in small cell lung cancer based on bioinformatic strategy and human samples

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242194
Author(s):  
Xiuwen Chen ◽  
Li Wang ◽  
Xiaomin Su ◽  
Sen-yuan Luo ◽  
Xianbin Tang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Hub Genes ◽  
Human Samples

Small cell lung cancer (SCLC) is a carcinoma of the lungs with strong invasion, poor prognosis and resistant to multiple chemotherapeutic drugs. It has posed severe challenges for the effective treatment of lung cancer. Therefore, searching for genes related to the development and prognosis of SCLC and uncovering their underlying molecular mechanisms are urgent problems to be resolved. This study is aimed at exploring the potential pathogenic and prognostic crucial genes and key pathways of SCLC via bioinformatic analysis of public datasets. Firstly, 117 SCLC samples and 51 normal lung samples were collected and analyzed from three gene expression datasets. Then, 102 up-regulated and 106 down-regulated differentially expressed genes (DEGs) were observed. And then, functional annotation and pathway enrichment analyzes of DEGs was performed utilizing the FunRich. The protein-protein interaction (PPI) network of the DEGs was constructed through the STRING website, visualized by Cytoscape. Finally, the expression levels of eight hub genes were confirmed in Oncomine database and human samples from SCLC patients. It showed that CDC20, BUB1, TOP2A, RRM2, CCNA2, UBE2C, MAD2L1, and BUB1B were upregulated in SCLC tissues compared to paired adjacent non-cancerous tissues. These suggested that eight hub genes might be viewed as new biomarkers for prognosis of SCLC or to guide individualized medication for the therapy of SCLC.

scholarly journals Monastrol Targeted KIF11 Showed Potential Treatment Effective of Small Cell Lung Cancer

2019 ◽  
Author(s):  
Xinhui Wang ◽  
Shanshan Jiang ◽  
Baolin Zhou ◽  
Zhantao Liu ◽  
Ziling Liu
Keyword(s):  
Lung Cancer ◽  
Network Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Normal Lung ◽  
Small Cell Lung ◽  
Hub Genes ◽  
Vitro Assay

Abstract Objective: This study is to identify Small Cell Lung Cancer (SCLC) driver genes, annotate enrichment functions and key pathways, and also verify Monastrol therapeutic effect. Methods: The gene expression profiles of GSE40275 and GSE43346 was analyzed to identify the DEGs (Differentially Expressed Genes) between SCLC and the normal tissue. GO (Gene Ontology), KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis and PPI (Protein-protein interaction) network analysis were conducted to find out the enrichment functions, pathways and hub genes. Moreover, in vitro, MTT assay, colony-forming assay, and the scratch assay were performed to verify the effect of Monastrol. Results: There were common 129 up-regulated and 176 down-regulated DEGs between SCLC samples and normal lung samples. KIF11, NDC80 and PBK were identified as hub genes after PPI network analysis. The q-PCR results showed that genes KIF11, NDC80 and PBK consistently expressed higher in cancer cells than normal cell lines. And in vitro assay showed that Monastrol inhibited SCLC cellular viability, proliferation and migration (P < 0.01). Conclusion: KIF11, NDC80 and PBK were aberrantly expressed and could be potentially applied as diagnostic biomarkers, therapeutic targets and prognostic biomarkers. Monastrol was a promising drug in treatment of SCLC patients. Key words: bioinformatics; lung science; SCLC; Monastrol.

The Key microRNAs Regulated the Development of Non-small Cell Lung Cancer by Targeting TGF-β-induced epithelial–mesenchymal Transition

2019 ◽  
Vol 22 (4) ◽  
pp. 238-244 ◽  
Author(s):  
Gang Chen ◽  
Bo Ye
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Normal Lung ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition

Purpose: Epithelial-to-Mesenchymal Transition (EMT) was reported to play a key role in the development of Non-Small Cell Lung Cancer (NSCLC). The process of EMT is regulated by the changes of miRNAs expression. However, it is still unknown which miRNA changed the most in the process of canceration and whether these changes played a role in tumor development. Methods: A total of 36 SCLC patients treated in our hospital between 11th, 2015 and 10th, 2017 were enrolled. The samples of cancer tissues and paracancer tissues of patients were collected and analyzed. Then, the miRNAs in normal lung cells and NSCLC cells were also analyzed. In the presence of TGF-β, we transfected the miRNA mimics or inhibitor into NSCLC cells to investigate the role of the significantly altered miRNAs in cell migration and invasion and in the process of EMT. Results: MiR-330-3p was significantly up-regulated in NSCLC cell lines and tissues and miRNA- 205 was significantly down-regulated in NSCLC cell lines and NSCLC tissues. Transfected miRNA-205 mimics or miRMA-330-3p inhibitor inhibited the migration and invasion of NCIH1975 cell and restrained TGF-β-induced EMT in NSCLC cells. Conclusion: miRNA-330-3p and miRNA-205 changed the most in the process of canceration in NSCLC. Furthermore, miR-330-3p promoted cell invasion and metastasis in NSCLC probably by promoting EMT and miR-205 could restrain NSCLC likely by suppressing EMT.

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