Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, 100142, China.
State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, 100101, China.
Theranostics. 2022 Jun 6;12(10):4671-4683. doi: 10.7150/thno.74770. eCollection 2022.
Gastric cancer (GC) is preceded by a stepwise progression of precancerous gastric lesions. Distinguishing individuals with precancerous gastric lesions that have progression potential to GC is an important need. Perturbated lipid metabolism, particularly the dysregulation of lipogenesis, is involved in gastric carcinogenesis. We conducted the first prospective lipidomics study exploring lipidomic signatures for the risk of gastric lesion progression and early GC. Our two-stage study of targeted lipidomics enrolled 400 subjects from the National Upper Gastrointestinal Cancer Early Detection Program in China, including 200 subjects of GC and different gastric lesions in the discovery and validation stages. Of validation stage, 152 cases with gastric lesions were prospectively followed for the progression of gastric lesions for a median follow-up of 580 days (interquartile range 390-806 days). We examined the lipidomic signatures associated with the risk of advanced gastric lesions and their progression to GC. Our published tissue proteomic data were referred to further investigate highlighted lipids with their biologically related protein expression in gastric mucosa. We identified 11 plasma lipids significantly inversely associated with the risk of gastric lesion progression and GC occurrence. These lipids were integrated as latent profiles to identify 5 clusters of lipid expression that had distinct risk of gastric lesion progression. The latent profiles significantly improved the ability to predict the progression potential of gastric lesions (AUC: 0.82 vs 0.68, Delong's P = 4.6×10) and risk of early GC (AUC: 0.81 vs 0.55, P = 6.3×10). Significant associations were found between highlighted lipids, their biologically correlated proteins and the risk of GC, supporting the role of the pathways involving monocarboxylic acid metabolism and lipid transport and catabolic process in GC. Our study revealed the lipidomic signatures associated with the risk of gastric lesion progression and GC occurrence, exhibiting translational implications for GC prevention.
胃癌（GC）是由癌前胃病变的逐步进展引起的。区分具有进展为 GC 潜能的癌前胃病变患者是一项重要需求。脂质代谢紊乱，特别是脂肪生成的失调，参与了胃癌的发生。我们进行了首次前瞻性脂质组学研究，探索了脂质组学特征与胃病变进展和早期 GC 的风险。我们的靶向脂质组学两阶段研究纳入了来自中国国家上消化道癌早期检测计划的 400 名受试者，包括发现和验证阶段的 200 名 GC 患者和不同的胃病变患者。在验证阶段，152 例胃病变患者前瞻性随访胃病变进展，中位随访时间为 580 天（四分位距 390-806 天）。我们检查了与高级胃病变风险及其进展为 GC 相关的脂质组学特征。我们发表的组织蛋白质组学数据被引用，以进一步研究胃黏膜中具有生物学相关性的脂质及其蛋白表达。我们确定了 11 种与胃病变进展和 GC 发生风险呈显著负相关的血浆脂质。这些脂质被整合为潜在特征，以识别胃病变进展风险不同的 5 个脂质表达簇。潜在特征显著提高了预测胃病变进展潜力的能力（AUC：0.82 与 0.68，Delong's P = 4.6×10）和早期 GC 的风险（AUC：0.81 与 0.55，P = 6.3×10）。在有亮点的脂质、其生物学相关蛋白与 GC 风险之间发现了显著的相关性，支持涉及单羧酸代谢和脂质转运和分解代谢过程的途径在 GC 中的作用。我们的研究揭示了与胃病变进展和 GC 发生风险相关的脂质组学特征，为 GC 预防提供了转化意义。
