A Novel Immune-Related Prognostic Model for Response to Immunotherapy and Survival in Patients With Lung Adenocarcinoma

• Main Authors: Yujia Zheng, He Tian, Zheng Zhou, Chu Xiao, Hengchang Liu, Yu Liu, Liyu Wang, Tao Fan, Bo Zheng, Fengwei Tan, Qi Xue, Gengshu Gao, Chunxiang Li, Jie He
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-03-01
• Series: Frontiers in Cell and Developmental Biology
• Subjects: lung adenocarcinoma; immune infiltration; prognosis; immunotherapy; risk prediction model; signature
• Online Access: https://www.frontiersin.org/articles/10.3389/fcell.2021.651406/full

Lung adenocarcinoma is one of the most malignant diseases worldwide. The immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) have changed the paradigm of lung cancer treatment; however, there are still patients who are resistant. Further exploration of the immune infiltration status of lung adenocarcinoma (LUAD) is necessary for better clinical management. In our study, the CIBERSORT method was used to calculate the infiltration status of 22 immune cells in LUAD patients from The Cancer Genome Atlas (TCGA). We clustered LUAD based on immune infiltration status by consensus clustering. The differentially expressed genes (DEGs) between cold and hot tumor group were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. Last, we constructed a Cox regression model. We found that the infiltration of M0 macrophage cells and follicular helper T cells predicted an unfavorable overall survival of patients. Consensus clustering of 22 immune cells identified 5 clusters with different patterns of immune cells infiltration, stromal cells infiltration, and tumor purity. Based on the immune scores, we classified these five clusters into hot and cold tumors, which are different in transcription profiles. Hot tumors are enriched in cytokine–cytokine receptor interaction, while cold tumors are enriched in metabolic pathways. Based on the hub genes and prognostic-related genes, we developed a Cox regression model to predict the overall survival of patients with LUAD and validated in other three datasets. In conclusion, we developed an immune-related signature that can predict the prognosis of patients, which might facilitate the clinical application of immunotherapy in LUAD.