血浆代谢相关生物标志物检测在转移性结直肠癌诊断中的应用

Application of plasma metabolism-related biomarker detection in the diagnosis of metastatic colorectal cancer

目的通过靶向代谢组学探讨非转移性结直肠癌(nmCRC)和转移性结直肠癌(mCRC)患者的新生物标志物和治疗策略。方法选取2022-01-01-2023-01-01山东省肿瘤医院招募的30例nmCRC患者和30例年龄和性别与之匹配的mCRC患者。采集nmCRC和mCRC患者血浆样本,使用液相色谱法-串联质谱法检测氨基酸、胆汁酸和脂肪酸的血浆代谢物,并分析其相关性及诊断价值。结果共检测到27种氨基酸、16种脂肪酸和9种胆汁酸,其中乙醇胺(P=0.017)、牛磺酸(P=0.003)和色氨酸(P=0.013)、甘氨胆酸(P=0.015)、C15∶0(P=0.001)、C17∶1(P=0.005)、C17∶0(P=0.037)、C18∶3(P=0.021)、C18∶2(P=0.007)、C20∶3(P=0.024)、C20∶1(P=0.011)、C22∶5(P=0.028)、C24∶1(P=0.017)表达下降。受试者工作特征曲线(ROC)分析显示13种代谢标志物诊断mCRC的曲线下面积(AUC)范围为0.668~0.809,可以很好地区分nmCRC和mCRC。其中GCA和CA19-9具有良好的相关性,r=0.736,P=0.036。nmCRC和mCRC患者平均CA19-9值分别为25.25±35.67和1020.56±2545.23,t=-2.142,P=0.036。CA19-9或GCA单独分析CRC肝转移患者AUC值分别为0.768和0.677,CA19-9和GCA联合分析时AUC值为0.828。结论代谢组学呈现了一种针对CRC的新颖无创识别方法,有望成为一种用于诊断mCRC的有效方法。

Objective To explore new biomarkers and treatment strategies for patients with non-metastatic colorectal cancer(nmCRC)and metastatic colorectal cancer(mCRC)through targeted metabolomics.Methods A total of 30 nmCRC patients and 30 mCRC patients matched with age and gender were recruited from Shandong Cancer Hospital from 2022-01-01to 2023-01-01.Plasma samples were collected from patients with nmCRC and mCRC.Plasma metabolites of amino acids,bile acids and fatty acids were measured using liquid chromatography-tandem mass spectrometry,then analyze their correlation and diagnostic value,Results A total of 27 amino acids,16 fatty acids and 9 bile acids were detected.Among them,the expression of ethanolamine(P=0.017),taurine(P=0.003),tryptophan(P=0.013),glycocholic acid(P=0.015),C15:0(P=0.001),C17:1(P=0.005),C17:0(P=0.037),C18:3(P=0.021),C18:2(P=0.007),C20:3(P=0.024),C20:1(P=0.011),C22:5(P=0.028)and C24:1(P=0.017)were decreased.Receiver operating characteristic curve(ROC)analysis showed that the area under the curve(AUC)of 13 metabolic markers in the diagnosis of mCRC ranged from 0.668 to 0.809,which could well distinguish nmCRC from mCRC.There was a good correlation between GCA and CA19-9(r=0.736,P=0.036).The mean CA19-9 values of nmCRC and mCRC patients were 25.25±35.67 and 1020.56±2545.23,respectively(t=-2.142,P=0.036).The AUC values of CA19-9 or GCA alone in CRC patients with liver metastases were 0.768 and 0.677,respectively,and the AUC value of CA19-9 combined with GCA was 0.828.Conclusion Metabolomics presents a novel non-invasive identification method for CRC,and is expected to be an effective method for the diagnosis of mCRC.