Identification of tumor antigens and immune subtypes of early-stage lung squamous cell carcinoma for mRNA vaccine development

Abstract In lung squamous cell carcinoma (LUSC), current mRNA vaccines show promising effect, despite lack of benefit for a large number of patients. We categorized the ideal population for mRNA vaccines and explored available targets. Leucine-rich repeat LGI family member 2 (LGI2), amine oxidase copper containing 1 (AOC1), periostin (POSTN), and collagen type V alpha 2 (COL5A2) were discovered using mutation, survival and differential expression gene analyses. These four genes were over-expressed, mutant, and prognostic of survival in the TCGA-LUSC cohort. According to complete analyses, LUSC had immune exclusion and immune dysfunction. Lung squamous 1 (LSQ1) type exhibited a higher mutational load and copy number but no immune infiltration, whereas lung squamous 2 (LSQ2) tumors had a higher global methylation level and more fibroblasts but had less stemness, according to subtype analysis. Meanwhile, trajectory analysis revealed that the evolution of tumor microenvironment (TME) influenced prognosis. Consensus network was used to identify the molecular traits most relevant to disease development. Finally, we show that although LSQ1 is linked to immune exclusion and might be utilized for vaccination, LSQ2 is linked to immune dysfunction and could be used for immunotherapy. Our findings establish a theoretical basis for applying mRNA vaccines to LUSC.