TY - JOUR
T1 - Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile
AU - Narita, Daisuke
AU - Hishinuma, Eiji
AU - Ebina-Shibuya, Risa
AU - Miyauchi, Eisaku
AU - Matsukawa, Naomi
AU - Motoike, Ikuko N.
AU - Kinoshita, Kengo
AU - Koshiba, Seizo
AU - Tsukita, Yoko
AU - Notsuda, Hirotsugu
AU - Kimura, Nozomu
AU - Saito, Ryota
AU - Murakami, Koji
AU - Fujino, Naoya
AU - Ichikawa, Tomohiro
AU - Yamada, Mitsuhiro
AU - Tamada, Tsutomu
AU - Sugiura, Hisatoshi
N1 - Publisher Copyright:
© 2025 The Author(s)
PY - 2025/2
Y1 - 2025/2
N2 - Background: Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and more than 75,000 deaths annually in Japan. Several treatment options for advanced lung cancer are available, and the discovery of biomarkers will be useful for personalized medicine. Using metabolome analysis, we aimed to identify biomarkers for diagnosis and treatment response by examining the changes in metabolites associated with lung cancer progression. Methods: Plasma samples from patients with recurrent or metastatic non-small cell lung carcinomas diagnosed at Tohoku University Hospital between 2019 and 2024 were used in this study. Metabolomic analysis was performed using the Biocrates Life Sciences MxP Quant 500 kit. Multivariate, principal component, and orthogonal partial least squares discriminant analyses were performed. Results: The triglyceride and phosphatidylcholine concentrations were higher in the patients with early than in those with advanced lung adenocarcinomas. However, the cholesterol ester concentrations were higher for the patients with advanced lung cancer. The concentrations of hexosylceramide were higher in patients with early lung adenocarcinoma than in those with squamous cell carcinoma. Relative to epidermal growth factor receptor (EGFR)-mutation negative cases, the EGFR-mutation positive cases showed marked differences between the ceramide and triglyceride concentrations. For the best therapeutic effect of EGFR-TKI treatment, the hexosylceramide (HexCer) (d18:1/24:0), ceramide (Cer) (d18:2/22:0), and ceramide (Cer) (d18:2/24:0) concentrations were higher for the stable and progressive disease groups. The concentrations of phosphatidylcholine (PC) ae C42:2, sphingomyelin (SM) C24:1, and lysophosphatidylcholine (lysoPC) a C18:2 were higher in the partial response group treated with immune checkpoint inhibitors and chemotherapy. Conclusion: Metabolomic analysis may be useful for the diagnosis and treatment of lung cancer and may provide clues for new therapeutic strategies. PC ae C42:2, SM C24:1, and lysoPC a C18:2 can serve as predictive biomarkers for monitoring the therapeutic effects of the combination of immune checkpoint inhibitors and chemotherapy.
AB - Background: Lung cancer is the deadliest disease globally, with more than 120,000 diagnosed cases and more than 75,000 deaths annually in Japan. Several treatment options for advanced lung cancer are available, and the discovery of biomarkers will be useful for personalized medicine. Using metabolome analysis, we aimed to identify biomarkers for diagnosis and treatment response by examining the changes in metabolites associated with lung cancer progression. Methods: Plasma samples from patients with recurrent or metastatic non-small cell lung carcinomas diagnosed at Tohoku University Hospital between 2019 and 2024 were used in this study. Metabolomic analysis was performed using the Biocrates Life Sciences MxP Quant 500 kit. Multivariate, principal component, and orthogonal partial least squares discriminant analyses were performed. Results: The triglyceride and phosphatidylcholine concentrations were higher in the patients with early than in those with advanced lung adenocarcinomas. However, the cholesterol ester concentrations were higher for the patients with advanced lung cancer. The concentrations of hexosylceramide were higher in patients with early lung adenocarcinoma than in those with squamous cell carcinoma. Relative to epidermal growth factor receptor (EGFR)-mutation negative cases, the EGFR-mutation positive cases showed marked differences between the ceramide and triglyceride concentrations. For the best therapeutic effect of EGFR-TKI treatment, the hexosylceramide (HexCer) (d18:1/24:0), ceramide (Cer) (d18:2/22:0), and ceramide (Cer) (d18:2/24:0) concentrations were higher for the stable and progressive disease groups. The concentrations of phosphatidylcholine (PC) ae C42:2, sphingomyelin (SM) C24:1, and lysophosphatidylcholine (lysoPC) a C18:2 were higher in the partial response group treated with immune checkpoint inhibitors and chemotherapy. Conclusion: Metabolomic analysis may be useful for the diagnosis and treatment of lung cancer and may provide clues for new therapeutic strategies. PC ae C42:2, SM C24:1, and lysoPC a C18:2 can serve as predictive biomarkers for monitoring the therapeutic effects of the combination of immune checkpoint inhibitors and chemotherapy.
KW - Lung cancer
KW - Metabolomics
UR - http://www.scopus.com/inward/record.url?scp=85216240809&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85216240809&partnerID=8YFLogxK
U2 - 10.1016/j.lungcan.2025.108082
DO - 10.1016/j.lungcan.2025.108082
M3 - Article
C2 - 39884221
AN - SCOPUS:85216240809
SN - 0169-5002
VL - 200
JO - Lung Cancer
JF - Lung Cancer
M1 - 108082
ER -
