Identification and Functional Analysis of Individual-Specific Subpathways in Lung Adenocarcinoma

Small molecular networks within complex pathways are defined as subpathways. The identification of patient-specific subpathways can reveal the etiology of cancer and guide the development of personalized therapeutic strategies. The dysfunction of subpathways has been associated with the occurrence and development of cancer. Here, we propose a strategy to identify aberrant subpathways at the individual level by calculating the edge score and using the Gene Set Enrichment Analysis (GSEA) method. This provides a novel approach to subpathway analysis. We applied this method to the expression data of a lung adenocarcinoma (LUAD) dataset from The Cancer Genome Atlas (TCGA) database. We validated the effectiveness of this method in identifying LUAD-relevant subpathways and demonstrated its reliability using an independent Gene Expression Omnibus dataset (GEO). Additionally, survival analysis was applied to illustrate the clinical application value of the genes and edges in subpathways that were associated with the prognosis of patients and cancer immunity, which could be potential biomarkers. With these analyses, we show that our method could help uncover subpathways underlying lung adenocarcinoma.