Department of Applied Chemistry, Institute of Natural Science, Kyung Hee University, Yongin, 17104, Republic of Korea.
Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul, 02454, Republic of Korea.
Nat Commun. 2024 Nov 23;15(1):10164. doi: 10.1038/s41467-024-54434-4.
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.
非小细胞肺癌（NSCLC）在组织学上可分为肺腺癌（LUAD）和肺鳞状细胞癌（LSCC）。然而，一些肿瘤在组织学上存在模糊性，其他病理生理特征或微环境因素可能更为突出。在这里，我们报告了使用来自韩国 NSCLC 队列的 229 名患者和之前多组学研究的 462 名患者的数据进行的综合多组学分析。组织学检查显示有五个分子亚型，其中一个是 NSCLC 亚型，其 PI3K-Akt 通路上调，无论任何特定的 NSCLC 组织学如何，其转移比例较高，生存结局较差。增殖亚型存在于 LUAD 和 LSCC 中，与全基因组加倍（WGD）事件有很强的关联。对免疫微环境的全面描述揭示了不同分子亚型的各种免疫细胞组成和新抗原负荷，这些都预示着不同的预后。免疫亚型表现出热肿瘤富集状态和辅助治疗的更高疗效。
