Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment

Kyu Jin Song, Seunghyuk Choi, Kwoneel Kim, Hee Sang Hwang, Eunhyong Chang, Ji Soo Park, Seok Bo Shim, Seunghwan Choi, Yong Jin Heo, Woo Ju An, Dae Yeol 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 and Kwang Pyo Kim ()
Additional contact information
Kyu Jin Song: Kyung Hee University
Seunghyuk Choi: Hanyang University
Kwoneel Kim: Kyung Hee University
Hee Sang Hwang: University of Ulsan College of Medicine, Asan Medical Center
Eunhyong Chang: Korea University
Ji Soo Park: Kyung Hee University
Seok Bo Shim: Kyung Hee University
Seunghwan Choi: Korea University
Yong Jin Heo: Korea University
Woo Ju An: Kyung Hee University
Dae Yeol Yang: Kyung Hee University
Kyung-Cho Cho: Kyung Hee University
Wonjun Ji: Asan Medical Center, University of Ulsan College of Medicine
Chang-Min Choi: Asan Medical Center, University of Ulsan College of Medicine
Jae Cheol Lee: Asan Medical Center, University of Ulsan College of Medicine
Hyeong-ryul Kim: University of Ulsan College of Medicine
Jiyoung Yoo: University of Ulsan Asan Medical Center
Hee-Sung Ahn: University of Ulsan Asan Medical Center
Gang-Hee Lee: Korea University
Chanwoong Hwa: Korea University
Seoyeon Kim: Korea University
Kyunggon Kim: University of Ulsan Asan Medical Center
Min-Sik Kim: DGIST
Eunok Paek: Hanyang University
Seungjin Na: Hanyang University
Se Jin Jang: University of Ulsan College of Medicine, Asan Medical Center
Joon-Yong An: Korea University
Kwang Pyo Kim: Kyung Hee University

Nature Communications, 2024, vol. 15, issue 1, 1-25

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54434-4

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