The Immune Heterogeneity Between Pulmonary Adenocarcinoma and Squamous Cell Carcinoma: A Comprehensive Analysis Based on lncRNA Model

Abstract

Adenocarcinoma (AD) and squamous cell carcinoma (SCC) are both classified as major forms of non-small cell lung cancer, but differences in clinical prognoses and molecular mechanisms are remarkable. Recent studies have supported the importance of understanding immune status in that it influences clinical outcomes of cancer, and immunotherapies based on the theory of “immune editing” have had notable clinical success. Our study aimed to identify specific long non-coding (lnc) RNAs that control key immune-related genes and to use them to construct risk models for AD and SCC. Risk scores were used to separate patients into high- and low-risk groups, and we validated the prognostic significance of both risk scores with our own cohorts. A Gene Set Enrichment Analysis suggested that the immune responses of patients in the AD high-risk group and the SCC low-risk group tended to be weakened. Evaluation of immune infiltration revealed that the degree of infiltration of dendritic cells is of particular importance in AD. In addition, prediction of responses to immune checkpoint inhibitor (ICI) treatments, based on the T Cell Immune Dysfunction and Exclusion and immunophenoscore models, indicated that deterioration of the immune microenvironment is due mainly to T cell exclusion in AD patients and T cell dysfunction in SCC patients and that high-risk patients with SCC might benefit from ICI treatment. The prediction of downstream targets via The Cancer Proteome Atlas and RNA-seq analyses of a transfected lung cancer cell line indicated that the lncRNA LINC00996 is a potential therapeutic target in AD.