Abstract 3496: Transcriptomic classification of lung adenocarcinoma identifies a novel subgroup with a poor survival prognosis

Abstract Lung adenocarcinoma is one-half of all lung cancer and the third deadliest cancer in the world. The traditional classification of lung adenocarcinoma involves invasiveness, growth pattern, presence of mucin, and other histological features. However, this classification provides limited prognostic predictability. Molecular profiles based The Cancer genome Atlas lung adenocarcinoma cohort classified the tumors into the terminal respiratory unit (TRU), proximal proliferative (PP), and proximal infiltrative (PI) based on unsupervised classification, which did not address clinical applicability to the classification. Here, we developed an unsupervised classification with Density-based UMAP (DBU), which identified four transcriptomic profiles for lung adenocarcinoma (Transcriptomic profile, TP1-TP4). We identified a gene signature with 299 genes to develop a supervised classifier, called Ensemble Transcriptomic classifier (ETC), to identify these four subgroups within the total cohort. All TP1 is PI. TP2 is 49.0% TFU and 45.0% PP. TP3 is 76.2% PI and 23.8% PP. TP4 is 54.5% TFU and 45.5% PI. TP1 is characterized by neuroendocrine-like features and clusters with large cell neuroendocrine tumors in cluster analysis. TP3 is squamous-like enriched with cell cycle and DNA repair high and worse prognosis and groups with squamous cell carcinoma in cluster analysis. TP2 has high immune cell infiltration, and TP4 showed low mutational burden and low immune cell infiltration. We validated these subgroups identified in the TCGA cohort in a microarray meta-dataset with DBU, ETC. This classification showed four subgroups in lung adenocarcinoma, which shows potential clinical actionable findings. Citation Format: Khaled Bin Satter, Paul MH Tran, Lynn KH Tran, John Nechtman, Nikhil Patel, Bruno Santos, Diane Hopkins, Nagla Abdel Karim, Jin-Xiong She, Sharad B. Purohit. Transcriptomic classification of lung adenocarcinoma identifies a novel subgroup with a poor survival prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3496.