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; Kwang Pyo Kim

doi:10.1038/s41467-024-54434-4

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 HwaSeoyeon Kim, Kyunggon Kim, Min Sik Kim, Eunok Paek, Seungjin Na, Se Jin Jang, Joon Yong An, Kwang Pyo Kim

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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.

Original language	English
Article number	10164
Journal	Nature Communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-54434-4
Publication status	Published - Dec 2024

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Publisher Copyright:
© The Author(s) 2024.

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10.1038/s41467-024-54434-4

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Song, K. J., Choi, S., Kim, K., Hwang, H. S., Chang, E., Park, J. S., Shim, S. B., Choi, S., Heo, Y. J., An, W. J., Yang, D. Y., Cho, K. C., Ji, W., Choi, C. M., Lee, J. C., Kim, H. R., Yoo, J., Ahn, H. S., Lee, G. H., ... Kim, K. P. (2024). Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment. Nature Communications, 15(1), Article 10164. https://doi.org/10.1038/s41467-024-54434-4

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

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.",

author = "Song, {Kyu Jin} and Seunghyuk Choi and Kwoneel Kim and Hwang, {Hee Sang} and Eunhyong Chang and Park, {Ji Soo} and Shim, {Seok Bo} and Seunghwan Choi and Heo, {Yong Jin} and An, {Woo Ju} and Yang, {Dae Yeol} and Cho, {Kyung Cho} and Wonjun Ji and Choi, {Chang Min} and Lee, {Jae Cheol} and Kim, {Hyeong Ryul} and Jiyoung Yoo and Ahn, {Hee Sung} and Lee, {Gang Hee} and Chanwoong Hwa and Seoyeon Kim and Kyunggon Kim and Kim, {Min Sik} and Eunok Paek and Seungjin Na and Jang, {Se Jin} and An, {Joon Yong} and Kim, {Kwang Pyo}",

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year = "2024",

month = dec,

doi = "10.1038/s41467-024-54434-4",

language = "English",

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Song, KJ, Choi, S, Kim, K, Hwang, HS, Chang, E, Park, JS, Shim, SB, Choi, S, Heo, YJ, An, WJ, Yang, DY, Cho, KC, Ji, W, Choi, CM, Lee, JC, Kim, HR, Yoo, J, Ahn, HS, Lee, GH, Hwa, C, Kim, S, Kim, K, Kim, MS, Paek, E, Na, S, Jang, SJ, An, JY & Kim, KP 2024, 'Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment', Nature Communications, vol. 15, no. 1, 10164. https://doi.org/10.1038/s41467-024-54434-4

TY - JOUR

T1 - Proteogenomic analysis reveals non-small cell lung cancer subtypes predicting chromosome instability, and tumor microenvironment

AU - Song, Kyu Jin

AU - Choi, Seunghyuk

AU - Kim, Kwoneel

AU - Hwang, Hee Sang

AU - Chang, Eunhyong

AU - Park, Ji Soo

AU - Shim, Seok Bo

AU - Choi, Seunghwan

AU - Heo, Yong Jin

AU - An, Woo Ju

AU - Yang, Dae Yeol

AU - Cho, Kyung Cho

AU - Ji, Wonjun

AU - Choi, Chang Min

AU - Lee, Jae Cheol

AU - Kim, Hyeong Ryul

AU - Yoo, Jiyoung

AU - Ahn, Hee Sung

AU - Lee, Gang Hee

AU - Hwa, Chanwoong

AU - Kim, Seoyeon

AU - Kim, Kyunggon

AU - Kim, Min Sik

AU - Paek, Eunok

AU - Na, Seungjin

AU - Jang, Se Jin

AU - An, Joon Yong

AU - Kim, Kwang Pyo

PY - 2024/12

Y1 - 2024/12

N2 - 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.

AB - 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.

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DO - 10.1038/s41467-024-54434-4

M3 - Article

C2 - 39580524

AN - SCOPUS:85210081553

SN - 2041-1723

VL - 15

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 10164

ER -

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

Abstract

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