International Journal of General Medicine (Apr 2022)
Identifying Molecular Subtypes and 6-Gene Prognostic Signature Based on Hypoxia for Optimizing Targeted Therapies in Non-Small Cell Lung Cancer
Abstract
Jingrong Lin,1 Shujiao Chen,2 Linling Xiao,3 Ziyan Wang,1 Yanqing Lin,1 Shungui Xu1 1Department of Respiratory Medicine, The Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fujian, 35003, People’s Republic of China; 2Academic Affairs Office, People’s Hospital Affiliated to Fujian University of Traditional Chinese Medicine, Fujian, 35003, People’s Republic of China; 3The First Clinical Medical College, Fujian University of Traditional Chinese Medicine, Fujian, 35003, People’s Republic of ChinaCorrespondence: Shungui Xu, Department of Respiratory Medicine, Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fujian, 35003, People’s Republic of China, Email [email protected]: Non-small cell lung cancer (NSCLC) accounts for a great number of all lung cancer cases. Hypoxia, one of the hallmarks in solid cancer, is closely involved in cancer cell progression and migration. This study aimed to develop a molecular subtyping system based on hypoxia-related genes and construct a prognostic model for NSCLC patients.Methods: Unsupervised consensus clustering was used to classify molecular subtypes. Mutation and immune analyses were conducted to compare differences among the molecular subtypes. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) analysis, and step Akaike information criterion (stepAIC) were performed to screen prognostic genes.Results: Two molecular subtypes (C1 and C2) were identified based on hypoxia-related genes and showed significant differences in survival, enriched pathways, tumor microenvironment (TME), and sensitivity to immunotherapy and chemotherapy. Interestingly, C1 subtype had better survival and response to targeted therapies. Oncogenic pathways, such as hypoxia, epithelial mesenchymal transition (EMT), NOTCH signaling, and p53 signaling pathways were more enriched in C2 subtype. A 6-gene prognostic model with robust ability was developed to classify NSCLC patients into high-risk and low-risk groups.Conclusion: The novel molecular subtypes could assist personalized therapies to select suitable patients. The six prognostic genes may be novel targets for further understanding mechanisms of NSCLC development associated with hypoxia and exploiting novel targeted therapies.Keywords: non-small cell lung cancer, hypoxia, molecular subtypes, tumor microenvironment, immunotherapy, prognostic genes, bioinformatics analysis
