PO-152 Differentiation of lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) by gene co-expression analysis of notch signalling targets

Introduction Lung carcinomas are very aggressive malignancies, which remain leading cancer-related cause of death among men and women worldwide. Regarding histological classification LUSC and LUAD account for the majority of lung tumours among non-small cell carcinomas (NSCLC). Notch signalling is evolutionarily-conserved pathway that regulates many cellular processes such as proliferation, differentiation and epithelial-to-mesenchymal transition (EMT). To date, aberrant Notch signalling has been linked with wide variety of malignancies, including lung tumours. However the association between co-expression profile of Notch downstream effector and lung cancer subtypes remains unclear. Therefore the aim of our study was to investigate functional gene co-expression networks to search for candidate biomarkers or therapeutic targets. Material and methods In our analysis we used RNASeq expression and clinical data downloaded from The Cancer Genome Atlas (TGCA). Gene Set Enrichment Analysis (GSEA) performed for canonical pathways pointed to Notch pathway as one of the most significant. Subsequently we analysed expression of downstream Notch effectors, 2949 HES/HEY transcription factors targets. To this extent used Weighted Gene Co-expression Network Analysis (WGCNA) to find differences in gene expression profile between LUSC and LUAD. Results and discussions The analysis of Notch pathway downstream targets which expression is regulated by HES/HEY transcription factors, identified 9 gene modules highly correlated with cancer type, with two of them as the most promising. Functional analysis revealed that among the differentially expressed genes were those involved in proliferation, cell cycle regulation, DNA repair, EMT, adhesion and metabolic processes, for example: TP63, PIK3CA, ADAM23, DLG1, FXR1, SENP5, TTK, BIRC5, KIF18A, KIF14, KIF4A, MCM4, MCM10. For one module the highly connected hub gene is TP63, acts as oncogene in many tumour types including squamous cell carcinomas, and for the second module is KIF4A. Interestingly, all listed genes were found to be overexpressed in LUSC and downexpressed in LUAD. Conclusion Our analysis could be valuable for better understanding of the molecular mechanism of lung carcinoma as well as Notch signalling in lung cancer with emphasis of pathway gene expression as useful biomarker for differentiating cancer progression in lung cancer subtypes. Acknowledgment This study was founded by the National Science Centre, Poland nr 2016/23/N/NZ2/02575 and Medical University of Lodz 503/0-078-02/503-01-004