Early Stage Finding of an Immune-Enhanced Genetic Subtype of Nonsmall Cell Lung Cancer Related with T-Cell Depletion

BACKGROUND: Molecular categorization of lung cancer in medical care is becoming increasingly important on a regular basis. One of the molecular classifications of NSCLC (early-stage NSCLC) supports that tumors of different biological varieties differ in terms of their genomes and clinical characteristics. METHODS: Based on published immune cell signatures and early-stage NSCLC gene expression data including cancer genome maps, we used consensus cluster analysis to identify immune molecular subtypes associated with early-stage NSCLC expression subtypes. These subtypes were correlated with early-stage NSCLC expression subtypes. Next, applying a wide range of statistical techniques, we evaluated the link between molecular subtypes and clinical features, immunological microenvironment, and immunotherapy reactivity. Molecular subtypes were defined as a classification of cancerous cells. RESULTS: Multiple RNAseq cross-platform datasets of immune genes were used to identify two molecular subtypes (C1 and C2) of NSCLC, with C1 showing a more favorable prognosis than C2. The results were validated on the CSE datasets. In terms of clinical characteristics, C2 subtype samples with a worse prognosis showed a more advanced tumor stage and higher mortality. C2 showed immuno-infiltrative characteristics but had depletion of T-cells. Biological functions such as EMT were enriched on C2. A low TIDE score in C1 indicated that C1 samples could benefit from taking immunotherapy. C2 were more susceptible to standard chemotherapeutic treatments such paclitaxel, cisplatin, sorafenib, crizotinib, and erlotinib. CONCLUSION: According to our findings, early-stage NSCLC patients may benefit from receiving treatment with immune checkpoint blockade therapy.