Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment
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.
Authors
- Hee‐Sung Ahn (ORCID: https://orcid.org/0000-0003-2241-6536)
- Seok Bo Shim
- Kwoneel Kim (ORCID: https://orcid.org/0000-0002-4221-3421)
- Hee Sang Hwang (ORCID: https://orcid.org/0000-0001-9486-9214)
- Chang‐Min Choi (ORCID: https://orcid.org/0000-0002-2881-4669)
- Joon‐Yong An (ORCID: https://orcid.org/0000-0001-8839-6297)
- Se Jin Jang (ORCID: https://orcid.org/0000-0001-8239-4362)
- Kyu Jin Song
- Kyunggon Kim (ORCID: https://orcid.org/0000-0002-3072-5331)
- Wonjun Ji (ORCID: https://orcid.org/0000-0001-7164-2770)
- Seunghwan Choi
- Yong Jin Heo
- Wei An (ORCID: https://orcid.org/0000-0002-8625-4209)
- Min‐Sik Kim (ORCID: https://orcid.org/0000-0001-7317-5360)
- Seoyeon Kim (ORCID: https://orcid.org/0000-0001-9184-7087)
- Gang‐Hee Lee (ORCID: https://orcid.org/0000-0001-8093-0395)
- Jae Cheol Lee (ORCID: https://orcid.org/0000-0001-5963-0259)
- Eunok Paek (ORCID: https://orcid.org/0000-0003-3655-9749)
- Dae Yul Yang (ORCID: https://orcid.org/0000-0002-7331-302X)
- Seungjin Na (ORCID: https://orcid.org/0000-0002-5159-2048)
- Kwang Pyo Kim (ORCID: https://orcid.org/0000-0003-0095-3787)
- Sang-Heul Choi (ORCID: https://orcid.org/0000-0003-3600-1868)
- Chanwoong Hwa
- Ji Soo Park (ORCID: https://orcid.org/0000-0002-0522-7736)
- Kyung Cho Cho
- Hyeong-Ryul Kim
- Eunhyong Chang
- Jiyoung Yoo
Institutions
- Ulsan College (KR)
- Daegu Gyeongbuk Institute of Science and Technology (KR)
- Korea University (KR)
- Asan Medical Center (KR)
- Kyung Hee University (KR)
- University of Ulsan (KR)
- Kyung Hee University Medical Center (KR)
- Korea Basic Science Institute (KR)
- Hanyang University (KR)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-23
- DOI
- https://doi.org/10.1038/s41467-024-54434-4
- Citations
- 28
- Primary Topic
- Ferroptosis and cancer prognosis
- Type
- article
- Field-Weighted Citation Impact
- 11.73
Funders
- National Research Foundation
- Kyung Hee University
- Korea University
- National Research Foundation of Korea
- Daegu Gyeongbuk Institute of Science and Technology
- Ministry of Science and ICT, South Korea
- National Cancer Institute