Hu Zuojian, Shen Fenglin, Liu Yang, Zhong Ziqing, Chen Yongling, Xia Zhiyuan, Mo Cuiju, Yu Hongxiu
Shanghai Stomatological Hospital & School of Stomatology & Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Mol Oncol. 2025 Jun;19(6):1737-1750. doi: 10.1002/1878-0261.13791. Epub 2025 Jan 3.
Colorectal cancer (CRC) is a prevalent malignant tumor worldwide, with a high mortality rate due to its complex etiology and limited early screening techniques. This study aimed to identify potential biomarkers for early detection of CRC utilizing targeted metabolite profiling of platelet-rich plasma (PRP). Based on multiple reaction monitoring (MRM) mode, liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis identified metabolites in PRP collected from patients with CRC (n = 70) and healthy controls (n = 30). A total of 302 metabolites were identified and quantified in this study, including various categories such as lipids, lipid mediators, amino acids, and derivatives, organic acids and derivatives, nucleotides and derivatives, alkaloids, carbohydrates, vitamins and derivatives, and others. The differential analysis revealed that five carbohydrates and organic acids (lactose, glycerol-3-phosphate, 2-hydroxyglutaric acid, isocitric acid, and citric acid) involved in the carbohydrate metabolism pathway displayed consistent upregulation within PRP derived from patients with CRC. To further validate the abundance of differential metabolites, 10 pairs of CRC tissues, adjacent tissues, and matched PRP were collected. Ultimately, five carbohydrate metabolites were validated in PRP, and compared with carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA199), the five carbohydrate metabolites significantly improved the specificity of differentiating patients with CRC from healthy controls. Furthermore, the diagnostic efficacy of the combined five-carbohydrate metabolite panel was superior to that of individual metabolites, CEA and CA199. The sensitivity, specificity, and AUC of the metabolite panel in distinguishing patients with CRC from healthy controls were 90.00%, 96.67%, and 0.961 (95% CI 0.922-0.998), respectively. Collectively, metabolomics was used to identify and validate differential metabolites in the PRP of CRC, which may serve as potential early screening markers for patients with CRC.
结直肠癌（CRC）是全球范围内一种常见的恶性肿瘤，因其病因复杂且早期筛查技术有限，死亡率很高。本研究旨在通过对富含血小板血浆（PRP）进行靶向代谢物谱分析，确定用于早期检测CRC的潜在生物标志物。基于多反应监测（MRM）模式，液相色谱串联质谱（LC-MS/MS）分析确定了从CRC患者（n = 70）和健康对照（n = 30）收集的PRP中的代谢物。本研究共鉴定并定量了302种代谢物，包括脂质、脂质介质、氨基酸及其衍生物、有机酸及其衍生物、核苷酸及其衍生物、生物碱、碳水化合物、维生素及其衍生物等各类物质。差异分析显示，参与碳水化合物代谢途径的5种碳水化合物和有机酸（乳糖、3-磷酸甘油、2-羟基戊二酸、异柠檬酸和柠檬酸）在CRC患者来源的PRP中呈现一致的上调。为进一步验证差异代谢物的丰度，收集了10对CRC组织、相邻组织及匹配的PRP。最终，在PRP中验证了5种碳水化合物代谢物，与癌胚抗原（CEA）和癌抗原19-9（CA199）相比，这5种碳水化合物代谢物显著提高了区分CRC患者与健康对照的特异性。此外，联合5种碳水化合物代谢物的诊断效能优于单个代谢物、CEA和CA199。该代谢物组合在区分CRC患者与健康对照时的敏感性、特异性和曲线下面积（AUC）分别为90.00%、96.67%和0.961（95%可信区间0.922 - 0.998）。总体而言，代谢组学用于鉴定和验证CRC患者PRP中的差异代谢物，这些代谢物可能作为CRC患者潜在的早期筛查标志物。
