Background: Lung pre-invasion lesion may be stable for quite long years. The molecular mechanism of the evolution from lung pre-invasive lesion to invasive adenocarcinoma requires further illustrated. Methods: We perform transcriptome sequencing in the paired of normal tissue and three evolution phases from pre-invasive to invasive lung adenocarcinomas: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC). Then we use systematic biology method to identify the Dynamic network biomarker (DNB) and the tipping point of lung adenocarcinomas early evolution. Different expressed Genes (DEGs) were defined as linear up-expressed or down-expressed through AIS to IAC. Finally, DNB genes and selected DEGs were combined for further bioinformatics analysis. Results: DNB analysis on the time series of lung adenocarcinomas evolution indicated MIA was the tipping point, with 144 DNB genes as driving factors. Then 170 up-expressed and 141 down-expressed DEGs were further identified. The combined analysis of DNB gene and DEGs indicated there were functionally enrichment in cell proliferation and epithelial-mesenchymal transition (EMT)-associated pathways. In particular, in the top-ranked DNB genes and DEGs, SPP1 positively regulated MMP11 with activated EMT associated pathway. Conclusion: SPP1 associated EMT pathway may be acted as the drive factor in the evolution from lung pre-invasive lesion to invasive adenocarcinoma.
BIO23-018: SPP1 Regulated EMT in the Evolution From Pre-Invasive to Invasive Lung Adenocarcinomas as Dynamic Network Biomarker
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