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Nat. Commun., Nov 23 2024, 15 (1) | https://doi.org/10.1038/s41467-024-54434-4
Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment
Kyu Jin Song1,2,23, Seunghyuk Choi3,23, Kwoneel Kim4,5,23, Hee Sang Hwang6,23, Eunhyong Chang7,8, Ji Soo Park4, Seok Bo Shim4, Seunghwan Choi9, Yong Jin Heo7, Woo Ju An1,2, Dae Yeol Yang5, Kyung-Cho Cho1,2, Wonjun Ji10, Chang-Min Choi10,11, Jae Cheol Lee11, Hyeong-ryul Kim12, Jiyoung Yoo13, Hee-Sung Ahn13, Gang-Hee Lee7,8, Chanwoong Hwa7,8, Seoyeon Kim7,8, Kyunggon Kim13,14,15, Min-Sik Kim16,17,18, Eunok Paek3,19,20, Seungjin Na3,21,24, Se Jin Jang6,22,24, Joon-Yong An7,8,9,24 & Kwang Pyo Kim1,2,24
1Department of Applied Chemistry, Institute of Natural Science, Kyung Hee University, Yongin 17104, Republic of Korea.
2Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul 02454, Republic of Korea.
3Department of Computer Science, Hanyang University, Seoul 04763, Republic of Korea.
4Department of Biology, Kyung Hee University, Seoul 02447, Republic of Korea.
5Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
6Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.
7Department of Integrated Biomedical and Life Science, Korea University, Seoul 02841, Republic of Korea.
8BK21FOUR R&E Center for Learning Health Systems, Korea University, Seoul 02841, Republic of Korea.
9School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea.
10Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
11Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
12Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Seoul, Korea.
13Department of Digital Medicine, BK21 Project, University of Ulsan Asan Medical Center, Seoul 05505, Republic of Korea.
14Convergence Medicine Research Center, Asan Institute for Life Sciences, Seoul 05505, Republic of Korea.
15Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea.
16Department of New Biology, DGIST, Daegu 42988, Republic of Korea.
17New Biology Research Center, DGIST, Daegu 42988, Republic of Korea.
18Center for Cell Fate Reprogramming and Control, DGIST, Daegu 42988, Republic of Korea.
19Department of Artificial Intelligence, Hanyang University, Seoul 04763, Republic of Korea.
20Institute for Artificial Intelligence Research, Hanyang University, Seoul 04763, Republic of Korea.
21Digital Omics Research Center, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
22SG Medical, Inc., 3-11, Ogeum-ro 13-gil, Songpa-gu, Seoul, Republic of Korea.
23These authors contributed equally: Kyu Jin Song, Seunghyuk Choi, Kwoneel Kim, Hee Sang Hwang.
24These authors jointly supervised this work: Seungjin Na, Se Jin Jang, Joon-Yong An, Kwang Pyo Kim.
Corresponding author
Correspondence to Kwang Pyo Kim.
1Department of Applied Chemistry, Institute of Natural Science, Kyung Hee University, Yongin 17104, Republic of Korea.
2Department of Biomedical Science and Technology, Kyung Hee Medical Science Research Institute, Kyung Hee University, Seoul 02454, Republic of Korea.
3Department of Computer Science, Hanyang University, Seoul 04763, Republic of Korea.
4Department of Biology, Kyung Hee University, Seoul 02447, Republic of Korea.
5Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Republic of Korea.
6Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea.
7Department of Integrated Biomedical and Life Science, Korea University, Seoul 02841, Republic of Korea.
8BK21FOUR R&E Center for Learning Health Systems, Korea University, Seoul 02841, Republic of Korea.
9School of Biosystems and Biomedical Sciences, College of Health Sciences, Korea University, Seoul 02841, Republic of Korea.
10Department of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
11Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
12Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Seoul, Korea.
13Department of Digital Medicine, BK21 Project, University of Ulsan Asan Medical Center, Seoul 05505, Republic of Korea.
14Convergence Medicine Research Center, Asan Institute for Life Sciences, Seoul 05505, Republic of Korea.
15Asan Institute for Life Sciences, Asan Medical Center, Seoul 05505, Republic of Korea.
16Department of New Biology, DGIST, Daegu 42988, Republic of Korea.
17New Biology Research Center, DGIST, Daegu 42988, Republic of Korea.
18Center for Cell Fate Reprogramming and Control, DGIST, Daegu 42988, Republic of Korea.
19Department of Artificial Intelligence, Hanyang University, Seoul 04763, Republic of Korea.
20Institute for Artificial Intelligence Research, Hanyang University, Seoul 04763, Republic of Korea.
21Digital Omics Research Center, Korea Basic Science Institute, Cheongju 28119, Republic of Korea.
22SG Medical, Inc., 3-11, Ogeum-ro 13-gil, Songpa-gu, Seoul, Republic of Korea.
23These authors contributed equally: Kyu Jin Song, Seunghyuk Choi, Kwoneel Kim, Hee Sang Hwang.
24These authors jointly supervised this work: Seungjin Na, Se Jin Jang, Joon-Yong An, Kwang Pyo Kim.
Corresponding author
Correspondence to 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.
논문정보
- Research article
- 2024년 11월 (BRIC 등록일 2024-11-25)
- 국내 연구진
- 의약학 > 유전 및 유전체의학
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