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

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, scrine protease inhibitor Kazal type 1, collagen type XI alpha 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 CCA AT/enhancer binding protein alpha transcription factor. These findings may provide further insight into the mechanisms of MMPs in invasive lung AC.