Department of Gastrointestinal Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Institute of Medical Science, Tokyo Medical University, Tokyo, Japan.
Cancer Sci. 2024 Sep;115(9):3089-3098. doi: 10.1111/cas.16256. Epub 2024 Jul 14.
Early detection of esophageal and gastric cancers is essential for patients' prognosis; however, optimal noninvasive screening tests are currently not available. Saliva is a biofluid that is readily available, allowing for frequent screening tests. Thus, we explored salivary diagnostic biomarkers for esophageal and gastric cancers using metabolomic analyses. Saliva samples were collected from patients with esophageal (n = 50) and gastric cancer (n = 63), and patients without cancer as controls (n = 20). Salivary metabolites were analyzed by liquid chromatography-mass spectrometry to identify salivary biomarkers. We also examined the metabolic profiles of gastric cancer tissues and compared them with the salivary biomarkers. The sensitivity of the diagnostic models based on salivary biomarkers was assessed by comparing it with that of serum tumor markers. Additionally, using postoperative saliva samples collected from patients with gastric cancer, we analyzed the changes in the biomarkers' concentrations before and after surgery. Cytosine was detected as a salivary biomarker for gastric cancer, and cytosine, 2-oxoglutarate, and arginine were detected as salivary biomarkers for esophageal cancer. Cytidine, a cytosine nucleotide, showed decreased concentrations in gastric cancer tissues. The sensitivity of the diagnostic models for esophageal and gastric cancers was 66.0% and 47.6%, respectively, while that of serum tumor markers was 40%. Salivary cytosine concentration increased significantly postoperatively relative to the preoperative value. In summary, we identified salivary biomarkers for esophageal and gastric cancers, which showed diagnostic sensitivity at least comparable to that of serum tumor markers. Salivary metabolomic tests could be promising screening tests for these types of cancer.
早期发现食管癌和胃癌对患者的预后至关重要；然而，目前尚无最佳的非侵入性筛查试验。唾液是一种易于获得的生物流体，可以进行频繁的筛查试验。因此，我们使用代谢组学分析方法探索了用于食管癌和胃癌的唾液诊断生物标志物。收集了 50 例食管癌患者、63 例胃癌患者和 20 例无癌症患者的唾液样本。通过液相色谱-质谱法分析唾液代谢物以鉴定唾液生物标志物。我们还检查了胃癌组织的代谢谱，并将其与唾液生物标志物进行了比较。通过将基于唾液生物标志物的诊断模型的灵敏度与血清肿瘤标志物的灵敏度进行比较，评估了诊断模型的灵敏度。此外，我们使用从胃癌患者术后收集的唾液样本，分析了手术前后生物标志物浓度的变化。胞嘧啶被检测为胃癌的唾液生物标志物，而胞嘧啶、2-氧戊二酸和精氨酸被检测为食管癌的唾液生物标志物。胞嘧啶核苷，一种胞嘧啶核苷酸，在胃癌组织中显示出浓度降低。食管癌和胃癌诊断模型的灵敏度分别为 66.0%和 47.6%，而血清肿瘤标志物的灵敏度为 40%。与术前值相比，术后唾液中胞嘧啶的浓度显著增加。总之，我们确定了食管癌和胃癌的唾液生物标志物，其诊断灵敏度至少与血清肿瘤标志物相当。唾液代谢组学测试可能是这些类型癌症有前途的筛查测试。
