Comprehensive Bioinformatics Analysis Identifies a Novel Cellular Senescence Associated Factor-Related Signature to Predict Prognosis and Efficacy of Immunotherapy in Lung Squamous Cell Carcinoma

Abstract

Abstract PURPOSE:Cellular senescence-related genes (SRS) plays a key role in tumorigenesis, progression, and immune regulation of cancer. We explored the role of SRS in the development of LUSC and how SRS regulates LUSC immunophenotype and predicted possible novel small molecule drugs. METHODS: We systematically analysised the clinical information and RNA-seq data related to patients with LUSC.Novel molecular subpopulations were identified using consensus clustering.Determined the tumor immune status of identified subgroups.Constructed and validated the prognostic risk model and clinical nomogram.Differential analysis of tumor stemness,immune checkpoints,and ICB responses was performed by SRS risk-score.For drug-screening and molecular docking, CMAP, LINCS, and AutodockVina technology were used. RESULTS: The survival rates of molecular subgroups differed significantly. The hyperimmune state was significant in the poorer prognosis subgroup. SRS affected the immune status of LUSC patients, and when combined with risk patterns and clinical characteristics, it could lead to a correct prediction of LUSC prognosis. High SRS risk-scores were associated with higher ICB responses, and immune checkpoint scores, and lower tumor stemness.Dasatinib may become a new targeted drug for LUSC. CONCLUSIONS:Overall, we identified prognostic SRS features in patients with LUSC, which were closely related to TIME. Further, reliable risk prediction models and clinical nomograms were constructed.The differences of ICB,tumor stemness,and immune checkpoint scores responses among patients with different risk scores were significant.Dasatinib was selected as a new small molecule for the potential treatment of LUSC[1].