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Basement membrane related genes in lung adenocarcinoma prognostic risk model based on single cell and bulk RNA
Jianan Yang1, Liang Wu2, Hongjuan Gong1
1Department of Respiratory and Critical Care Medicine, Haimen People's Hospital, Nantong, Jiangsu, China.
Background:
The heterogeneity of lung adenocarcinoma (LUAD) makes it challenging to fully comprehend its development. Basement Membrane (BM) promotes cell polarity and has a function in cell development.
Methods:
A single-cell transcriptional profile of LUAD was established to investigate the heterogeneity of the tumour microenvironment(TME). Subsequently, the cell differentiation status and intercellular communication analysis in LUAD microenvironment were analysed. A total of 250 genes were associated with the BM and involved in cell trajectory differentiation. Next, the variation in immune checkpoint gene expression levels and immunotherapy response between groups was analysed using consensus clustering. Weighted gene co-expression network analysis (WGCNA) was applied to identify genes from the modules that showed a strong correlation with clinical characteristics. Moreover, based on our thorough bioinformatics study, we established the prognostic signature of Basement Membrane -related genes (BMRGs) using genes with strong prognostic importance.
Results:
The MIF signalling pathway was found to be significantly activated in the TME. Cell differentiation trajectory analysis identified five subpopulations with distinct differentiation states. Every cluster has distinctive individual clinical characteristics and reflects a different immunological microenvironment. A prognosis model was created using six BMRGs with the most significant predictive power for survival.
Conclusion:
The model of risk score acts as a stand-alone prognostic factor, and the model is able to forecast patient prognoses with accuracy, which helps investigate more effective immunotherapy strategies.It also has a significant impact in TME.