Narita Daisuke, Hishinuma Eiji, Ebina-Shibuya Risa, Miyauchi Eisaku, Matsukawa Naomi, Motoike Ikuko N, Kinoshita Kengo, Koshiba Seizo, Tsukita Yoko, Notsuda Hirotsugu, Kimura Nozomu, Saito Ryota, Murakami Koji, Fujino Naoya, Ichikawa Tomohiro, Yamada Mitsuhiro, Tamada Tsutomu, Sugiura Hisatoshi
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Advanced Research Center for Innovations in Next Generation Medicine, Tohoku University, Sendai, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
Lung Cancer. 2025 Feb;200:108082. doi: 10.1016/j.lungcan.2025.108082. Epub 2025 Jan 8.
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.
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.
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.
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.
肺癌是全球最致命的疾病，在日本每年有超过12万例确诊病例和超过7.5万例死亡。晚期肺癌有多种治疗选择，生物标志物的发现将有助于个性化医疗。通过代谢组分析，我们旨在通过检查与肺癌进展相关的代谢物变化来识别诊断和治疗反应的生物标志物。
本研究使用了2019年至2024年在东北大学医院诊断为复发或转移性非小细胞肺癌患者的血浆样本。使用Biocrates Life Sciences MxP Quant 500试剂盒进行代谢组学分析。进行了多变量、主成分和正交偏最小二乘判别分析。
早期肺腺癌患者的甘油三酯和磷脂酰胆碱浓度高于晚期患者。然而，晚期肺癌患者的胆固醇酯浓度更高。早期肺腺癌患者的己糖神经酰胺浓度高于鳞状细胞癌患者。相对于表皮生长因子受体（EGFR）突变阴性病例，EGFR突变阳性病例的神经酰胺和甘油三酯浓度存在显著差异。为了使EGFR-TKI治疗获得最佳疗效，稳定和疾病进展组的己糖神经酰胺（HexCer）（d18:1/24:0）、神经酰胺（Cer）（d18:2/22:0）和神经酰胺（Cer）（d18:2/24:0）浓度更高。在接受免疫检查点抑制剂和化疗的部分缓解组中，磷脂酰胆碱（PC）ae C42:2、鞘磷脂（SM）C24:1和溶血磷脂酰胆碱（lysoPC）a C18:2的浓度更高。
代谢组分析可能有助于肺癌的诊断和治疗，并可能为新的治疗策略提供线索。PC ae C42:2、SM C24:1和lysoPC a C18:2可作为预测生物标志物，用于监测免疫检查点抑制剂和化疗联合治疗的效果。
