Zhong Wei, Liu Jian, Xie Junhua, Zhang Zhiyan, Gong Zhiwen, Yan Zhixiang, Cao Qingdong
Department of Thoracic Surgery and Lung Transplantation, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China.
Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, China.
BMC Cancer. 2025 Aug 1;25(1):1254. doi: 10.1186/s12885-025-14452-x.
Early diagnosis of esophageal squamous cell carcinoma (ESCC) is crucial for improving patient prognosis. Currently, the diagnosis of ESCC primarily relies on endoscopic biopsy. Salivary exosomes have shown great potential in non-invasive screening, but their proteomic and lipidomic characteristics remain to be reported.
Exosomes were isolated from salivary samples of 54 patients with ESCC and 62 healthy controls using ultracentrifugation, and subsequently subjected to non-targeted proteomic and lipidomic analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differentially expressed proteins and lipids in salivary exosomes were identified through differential analysis, and a comprehensive analysis of multi-omics data was performed using correlation analysis.
Significant proteomic and lipidomic differences were observed between ESCC patients and healthy controls. The proteomic characteristics of ESCC were primarily manifested in immune responses, disruption of tissue structural homeostasis, and enhanced antifungal and antimicrobial humoral immune responses. Through multi-omics analysis, we found that ESCC may regulate fatty acid metabolism by modulating epigenetic modifications, thereby influencing the oral immune microenvironment. Finally, a diagnostic model constructed using 28 lipid features achieved excellent diagnostic performance (Are Under the Curve = 1.000) for ESCC diagnosis.
Our study revealed significant alterations in the proteomic and lipidomic profiles of the oral microenvironment in ESCC patients, which may provide new insights into the development and progression of ESCC. We found that lipid features have high potential for diagnosing ESCC, providing support for further validation in larger cohorts.
食管鳞状细胞癌（ESCC）的早期诊断对于改善患者预后至关重要。目前，ESCC的诊断主要依赖于内镜活检。唾液外泌体在无创筛查中显示出巨大潜力，但其蛋白质组学和脂质组学特征仍有待报道。
采用超速离心法从54例ESCC患者和62例健康对照者的唾液样本中分离外泌体，随后通过液相色谱-串联质谱（LC-MS/MS）进行非靶向蛋白质组学和脂质组学分析。通过差异分析鉴定唾液外泌体中差异表达的蛋白质和脂质，并使用相关性分析对多组学数据进行综合分析。
ESCC患者与健康对照者之间存在显著的蛋白质组学和脂质组学差异。ESCC的蛋白质组学特征主要表现在免疫反应、组织结构稳态破坏以及抗真菌和抗菌体液免疫反应增强。通过多组学分析，我们发现ESCC可能通过调节表观遗传修饰来调控脂肪酸代谢，从而影响口腔免疫微环境。最后，利用28个脂质特征构建的诊断模型对ESCC诊断具有出色的诊断性能（曲线下面积=1.000）。
我们的研究揭示了ESCC患者口腔微环境蛋白质组学和脂质组学谱的显著改变，这可能为ESCC的发生和发展提供新的见解。我们发现脂质特征在诊断ESCC方面具有很高的潜力，为在更大队列中进行进一步验证提供了支持。
