Cai Ze-Rong, Wang Wen, Chen Di, Chen Hao-Jie, Hu Yan, Luo Xiao-Jing, Wang Yi-Ting, Pan Yi-Qian, Mo Hai-Yu, Luo Shu-Yu, Liao Kun, Zeng Zhao-Lei, Li Shan-Shan, Guan Xin-Yuan, Fan Xin-Juan, Piao Hai-Long, Xu Rui-Hua, Ju Huai-Qiang
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, P. R. China.
EMBO Mol Med. 2024 Dec;16(12):3089-3112. doi: 10.1038/s44321-024-00169-0. Epub 2024 Nov 14.
Early detection is warranted to improve prognosis of gastric cancer (GC) but remains challenging. Liquid biopsy combined with machine learning will provide new insights into diagnostic strategies of GC. Lipid metabolism reprogramming plays a crucial role in the initiation and development of tumors. Here, we integrated the lipidomics data of three cohorts (n = 944) to develop the lipid metabolic landscape of GC. We further constructed the serum lipid metabolic signature (SLMS) by machine learning, which showed great performance in distinguishing GC patients from healthy donors. Notably, the SLMS also held high efficacy in the diagnosis of early-stage GC. Besides, by performing unsupervised consensus clustering analysis on the lipid metabolic matrix of patients with GC, we generated the gastric cancer prognostic subtypes (GCPSs) with significantly different overall survival. Furthermore, the lipid metabolic disturbance in GC tissues was demonstrated by multi-omics analysis, which showed partially consistent with that in GC serums. Collectively, this study revealed an innovative strategy of liquid biopsy for the diagnosis of GC on the basis of the serum lipid metabolic fingerprints.
早期检测对于改善胃癌(GC)的预后很有必要,但仍然具有挑战性。液体活检与机器学习相结合将为GC的诊断策略提供新的见解。脂质代谢重编程在肿瘤的发生和发展中起着关键作用。在此,我们整合了三个队列(n = 944)的脂质组学数据,以构建GC的脂质代谢图谱。我们进一步通过机器学习构建了血清脂质代谢特征(SLMS),其在区分GC患者与健康供体方面表现出色。值得注意的是,SLMS在早期GC的诊断中也具有很高的效能。此外,通过对GC患者的脂质代谢矩阵进行无监督一致性聚类分析,我们生成了总生存期有显著差异的胃癌预后亚型(GCPSs)。此外,多组学分析证实了GC组织中的脂质代谢紊乱,这与GC血清中的情况部分一致。总体而言,本研究揭示了一种基于血清脂质代谢指纹的液体活检诊断GC的创新策略。