m6A‐ and immune‐related lncRNA signature confers robust predictive power for immune efficacy in lung squamous cell carcinoma

Abstract

Abstract Immune checkpoint blockade has revolutionized immunotherapy of lung squamous cell carcinoma (LUSC), but the effective rate is less than 30% attributing to no effective and reliable method for predicting immune response. However, the clinical value of N6‐methyladenosine (m6A) and immune‐related lncRNA (mirlncRNA) concerning immune efficacy remains unknown. First, we identified a packet of specific mirlncRNA. Based on this, patients with LUSC were optimally divided into mirlncRNA clusters A, B, and C. The mirlncRNA cluster A was categorized as an immune‐inflamed phenotype distinguished by infiltration of numerous immune cells such as tumor‐infiltrating lymphocyte cells and highlighted by pathways such as regulation of myeloid leukocyte differentiation, while clusters B and C were found to correspond to immune‐desert and immune‐excluded phenotypes, respectively. Furthermore, the immune‐inflamed phenotype was shown to possess the highest immune infiltration, the lowest chromatin accessibility, survival rates, half inhibitory concentration (IC50), and the best immune efficacy. Finally, risk scores derived from the mirlncRNA signature helped identify subgroups of patients who could significantly benefit from immunotherapy. Encouragingly, in the population with poor response to the three targeted drugs, the immune response of patients with low drug sensitivity is significantly improved, indicating the vitality of combined therapy. The mirlncRNA signature not only identifies molecular typing and distinguishes chromatin accessibility, but also further highlights the immune efficacy and drug sensitivity, which might contribute to developing a new strategy for immunotherapy‐based individualized treatment.

Keywords

• chromatin accessibility
• immune efficacy
• long‐chain non‐coding RNA
• lung squamous cell carcinoma
• N6‐methyladenosine (m6A) methylation