Histological and genetic features and therapeutic responses of lung cancers explored via the global analysis of their metabolome profile

IF 4.4 2区医学 Q1 ONCOLOGY Lung Cancer Pub Date : 2025-02-01 Epub Date: 2025-01-08 DOI:10.1016/j.lungcan.2025.108082

Daisuke Narita , Eiji Hishinuma , Risa Ebina-Shibuya , Eisaku Miyauchi , Naomi Matsukawa , Ikuko N. Motoike , Kengo Kinoshita , Seizo Koshiba , Yoko Tsukita , Hirotsugu Notsuda , Nozomu Kimura , Ryota Saito , Koji Murakami , Naoya Fujino , Tomohiro Ichikawa , Mitsuhiro Yamada , Tsutomu Tamada , Hisatoshi Sugiura

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Abstract

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.

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通过对其代谢组谱的全球分析，探索肺癌的组织学和遗传特征和治疗反应。

背景：肺癌是全球最致命的疾病，日本每年确诊病例超过12万例，死亡人数超过7.5万人。晚期肺癌的几种治疗方案是可用的，生物标志物的发现将有助于个性化医疗。利用代谢组学分析，我们旨在通过检查与肺癌进展相关的代谢物的变化来确定诊断和治疗反应的生物标志物。方法：本研究使用2019年至2024年在东北大学医院诊断的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。进行多元、主成分和正交偏最小二乘判别分析。结果：早期肺腺癌患者的甘油三酯和磷脂酰胆碱浓度高于晚期肺腺癌患者。然而，晚期肺癌患者的胆固醇酯浓度较高。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。对于EGFR-TKI治疗的最佳效果，在稳定组和进展组，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）浓度较高。在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的浓度较高。结论：代谢组学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可以作为监测免疫检查点抑制剂联合化疗治疗效果的预测性生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.