Abstract
BackgroundNon-small cell lung cancer (NSCLC) is the major type of lung cancer with high morbidity and poor prognosis. Erlotinib, an inhibitor of epidermal growth factor receptor (EGFR), has been clinically applied for NSCLC treatment. Nevertheless, the erlotinib acquired resistance of NSCLC occurs inevitably in recent years.MethodsThrough analyzing two microarray datasets, erlotinib resistant NSCLC cells microarray (GSE80344) and NSCLC tissue microarray (GSE19188), the differentially expressed genes (DEGs) were screened via R language. DEGs were then functionally annotated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, which up-regulated more than 2-folds in both datasets were further functionally analyzed by Oncomine, GeneMANIA, R2, Coremine, and FunRich.ResultsWe found that matrix metalloproteinase 1 (MMP1) may confer the erlotinib therapeutic resistance in NSCLC. MMP1 highly expressed in erlotinib-resistant cells and NSCLC tissues, and it associated with poor overall survival. In addition, MMP1 may be associated with COPS5 and be involve in an increasing transcription factors HOXA9 and PBX1 in erlotinib resistance.ConclusionsGenerally, these results demonstrated that MMP1 may play a crucial role in erlotinib resistance in NSCLC, and MMP1 could be a prognostic biomarker for erlotinib treatment.
Highlights
Lung cancer is the primary cancer-related death worldwide [1, 2]
To characterize the potential role of these significantly upregulated differentially expressed genes (DEGs), these DEGs were first performed for a Gene Ontology (GO) enrichment analysis, results were divided into three ontologies, including biological process (BP), cellular component (CC) and molecular function (MF), and the top five GO enrichment terms of each ontology were shown in Fig. 1c; Table S2
We revealed that matrix metalloproteinase 1 (MMP1) was overexpressed in Non-small cell lung cancer (NSCLC) tissues and erlotinib-resistant NSCLC cells, and it negatively associated with overall survival in NSCLC patients
Summary
Lung cancer is the primary cancer-related death worldwide [1, 2]. Non-small cell lung cancer (NSCLC) is the main type of lung cancer, including squamous cell carcinoma, adenocarcinoma, and large cell carcinoma, which accounts for approximately 85% of all cases [3,4,5]. Zhou et al Hereditas (2020) 157:32 inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, which is given for locally advanced or metastatic non-small cell lung cancer treatment [10,11,12]. It can block EGFR downstream signaling pathways such as the signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) pathway [13]. Non-small cell lung cancer (NSCLC) is the major type of lung cancer with high morbidity and poor prognosis. An inhibitor of epidermal growth factor receptor (EGFR), has been clinically applied for NSCLC treatment. The erlotinib acquired resistance of NSCLC occurs inevitably in recent years
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