Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment
Kyu Jin Song, Sang-Heul Choi, Kwoneel Kim, Hee Sang Hwang, Eunhyong Chang, Ji Soo Park, Seok Bo Shim, Seunghwan Choi, Yong Jin Heo, Wei An, Dae Yul Yang, Kyung Cho Cho, Wonjun Ji, Chang‐Min Choi, Jae Cheol Lee, Hyeong-Ryul Kim, Jiyoung Yoo, Hee‐Sung Ahn, Gang‐Hee Lee, Chanwoong Hwa, Seoyeon Kim, Kyunggon Kim, Min‐Sik Kim, Eunok Paek, Seungjin Na, Se Jin Jang, Joon‐Yong An, Kwang Pyo Kim, Joon‐Yong An, Kwang Pyo Kim, Kwang Pyo Kim
Abstract
Non-small cell lung cancer (NSCLC) is histologically classified into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LSCC). However, some tumors are histologically ambiguous and other pathophysiological features or microenvironmental factors may be more prominent. Here we report integrative multiomics analyses using data for 229 patients from a Korean NSCLC cohort and 462 patients from previous multiomics studies. Histological examination reveals five molecular subtypes, one of which is a NSCLC subtype with PI3K-Akt pathway upregulation, showing a high proportion of metastasis and poor survival outcomes regardless of any specific NSCLC histology. Proliferative subtypes are present in LUAD and LSCC, which show strong associations with whole genome doubling (WGD) events. Comprehensive characterization of the immune microenvironment reveals various immune cell compositions and neoantigen loads across molecular subtypes, which predicting different prognoses. Immunological subtypes exhibit a hot tumor-enriched state and a higher efficacy of adjuvant therapy. Subtyping of non-small cell lung cancer can be challenging based on pathology. Here, the authors utilise multi-omics analysis of 229 patients to identify further subtypes, and altered immune composition between subtypes.