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Identification of genes associated with matrix metalloproteinases in invasive lung adenocarcinoma.

ABSTRACT: The aim of the present study was to identify genes with similar function to that of matrix metalloproteinases (MMPs) in invasive lung adenocarcinoma (AC) and to screen the transcription factors that regulate MMPs. The gene expression dataset GSE2514, including 20 invasive lung AC samples and 19 adjacent normal lung samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the limma package in R. Genes with similar function to MMPs were identified by K-means clustering. Their correlations with MMPs were validated using Pearson correlation analysis. The expression of MMPs in lung cancer and normal tissues was evaluated by western blot analysis. Protein-protein interaction (PPI) network and transcriptional regulatory network analyses were performed with Retrieval of Interacting Genes and Database for Annotation, Visualization and Integrated Discovery, respectively. As a result, 269 DEGs were identified between invasive lung AC samples and normal lung samples, including 78 upregulated and 191 downregulated genes. Four MMPs (MMP1, MMP7, MMP9 and MMP12), which were upregulated in lung AC, were clustered into one group with other genes, including NAD(P)H quinone oxidoreductase 1, claudin 3 (CLDN3), S100 calcium-binding protein P, serine protease inhibitor Kazal type 1, collagen type XI ? 1 chain, periostin and desmoplakin (DSP), following cluster analysis. Pearson correlation analysis further confirmed correlations between MMP9-CLDN3, MMP9-DSP and MMP12-DSP. PPI network analysis also indicated multiple interactions between MMPs-associated genes. Furthermore, MMPs were commonly regulated by CCAAT/enhancer binding protein ? transcription factor. These findings may provide further insight into the mechanisms of MMPs in invasive lung AC.

SUBMITTER: Li W

PROVIDER: S-EPMC6006458 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Identification of genes associated with matrix metalloproteinases in invasive lung adenocarcinoma.

Li Weiqing W Zhang Xugang X Li Zhitian Z Jiang Fusheng F Zhao Hongwei H Wei Bo B

Oncology letters 20180510 1

The aim of the present study was to identify genes with similar function to that of matrix metalloproteinases (MMPs) in invasive lung adenocarcinoma (AC) and to screen the transcription factors that regulate MMPs. The gene expression dataset GSE2514, including 20 invasive lung AC samples and 19 adjacent normal lung samples, was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the limma package in R. Genes with similar function to MMP ...[more]

PMID: 29928392

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Project description:Lung cancer is the world's most common malignancies and ranks first among all cancer-related deaths. Lung adenocarcinoma (LUAD) is the most frequent histological type in lung cancer. Its pathogenesis has not yet been fully elucidated, so it is of great significance to explore related genes for elucidating the molecular mechanism involved in occurrence and development of LUAD.To explore the crucial genes associated with LUAD development and progression, microarray datasets GSE7670, GSE10072, and GSE31547 were acquired from the Gene Expression Omnibus (GEO) database. R language Limma package was adopted to screen the differentially expressed genes (DEGs). The clusterProfiler package was used for enrichment analysis and annotation of the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways for DEGs. The Search Tool for the Retrieval of Interacting Genes database (STRING) was used to construct the protein interaction network for DEGs, while Cytoscape was adopted to visualize it. The functional module was screened with Cytoscape's MCODE (The Molecular Complex Detection) plugin. The crucial genes associated with LUAD were identified by cytoHubba plugin. Kaplan-Meier plotter online tool was used to perform survival analysis of the hub gene.Three hundred twenty-one DEGs in total were screened, of which 105 were upregulated and 216 were downregulated. It was found that some GO terms and pathways (e.g., collagen trimer, extracellular structure organization, heparin binding, complement and coagulation cascades, malaria, protein digestion and absorption, and PPAR signaling pathway) were considerably enriched in DEGs. UBE2C, TOP2A, RRM2, CDC20, CCNB2, KIAA0101, BUB1B, TPX2, PRC1, and CDK1 were identified as crucial genes. Survival analysis showed that the overexpression of UBE2C, TOP2A, RRM2, CDC20, CCNB2, KIAA0101, BUB1B, TPX2, and PRC1 significantly reduced the overall survival of LUAD patients. One of the crucial genes: UBE2C was validated by immunohistochemistry to be upregulated in LUAD tissues.This study screened out potential biomarkers of LUAD, providing a theoretical basis for elucidating the pathogenesis and evaluating the prognosis of LUAD.

Project description:ObjectivesWe postulated that ventilation-perfusion (V/Q) relationships within the lung might influence where lung cancer occurs. To address this hypothesis we evaluated the location of lung adenocarcinoma, by both tumor lobe and superior-inferior regional distribution, and associated variables such as emphysema.Materials and methodsOne hundred fifty-nine cases of invasive adenocarcinoma and adenocarcinoma with lepidic features were visually evaluated to identify lobar or regional tumor location. Regions were determined by automated division of the lungs into three equal volumes: (upper region, middle region, or lower region). Automated densitometry was used to measure radiographic emphysema.ResultsThe majority of invasive adenocarcinomas occurred in the upper lobes (69%), with 94% of upper lobe adenocarcinomas occurring in the upper region of the lung. The distribution of adenocarcinoma, when classified as upper or lower lobe, was not different between invasive adenocarcinoma and adenocarcinoma with lepidic features (formerly bronchioloalveolar cell carcinoma, P = 0.08). Regional distribution of tumor was significantly different between invasive adenocarcinoma and adenocarcinoma with lepidic features (P = 0.001). Logistic regression analysis with the outcome of invasive adenocarcinoma histology was used to adjust for confounders. Tumor region continued to be a significant predictor (OR 8.5, P = 0.008, compared to lower region), whereas lobar location of tumor was not (P = 0.09). In stratified analysis, smoking was not associated with region of invasive adenocarcinoma occurrence (P = 0.089). There was no difference in total emphysema scores between invasive adenocarcinoma cases occurring in each of the three regions (P = 0.155). There was also no difference in the distribution of region of adenocarcinoma occurrence between quartiles of emphysema (P = 0.217).ConclusionInvasive adenocarcinoma of the lung is highly associated with the upper lung regions. This association is not related to smoking, history of COPD, or total emphysema. The regional distribution of invasive adenocarcinoma may be due to V/Q relationships or other local factors.

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Identification of genes associated with matrix metalloproteinases in invasive lung adenocarcinoma.

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Identification of genes associated with matrix metalloproteinases in invasive lung adenocarcinoma.

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