Institutes of Biomedical Sciences and The Fifth People's Hospital of Shanghai, Fudan University, Shanghai 200032, China.
Shanghai Dermatology Hospital, No. 1278th Baode Road, Jing'an District, Shanghai 200443, China.
Clin Chim Acta. 2020 Jul;506:214-221. doi: 10.1016/j.cca.2020.03.043. Epub 2020 Mar 31.
Pancreatic cancer (PC) is the fourth leading cause of cancer death because of its subtle clinical symptoms in the early stage. To discover particular serum metabolites as potential biomarkers to differentiate pancreatic carcinoma from benign disease (BD) is on urgent demand.
To comprehensively analyze serum metabolites obtained from 14 patients with PC, 10 patients with BD and 10 healthy individuals (normal control, NC), we separated the metabolites using both reversed-phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC). The data were acquired on a high-resolution quadrupole time-of-flight mass spectrometer operated in negative (ESI-) and positive (ESI+) ionization modes, respectively. Differential metabolites were selected by univariate (Student's t test) and multivariate (orthogonal partial least squares-discriminant analysis (OPLS-DA)) statistics. Sequential window acquisition of all theoretical spectra (SWATH) analysis was further utilized to validate the metabolites found in discovery stage. The receiver operator characteristics (ROC) curve analysis was performed to evaluate predictive clinical usefulness of 8 metabolites.
A total of 8 metabolites including taurocholic acid, glycochenodexycholic acid, glycocholic acid, L-glutamine, glutamic acid, L-phenylalanine, L-tryptophan, and L-arginine were identified and relatively quantified as differential metabolites for discriminating PC, BD and NC. The 8 metabolites and their combination discriminated PC from BD and NC with well-performed area under the curve (AUC) values, sensitivity and specificity.
Bile acids (especially taurocholic acid) performed to be potential biomarkers in PC diagnosis. Other amino acids (such as L-glutamine, glutamic acid, L-phenylalanine, L-tryptophan, and L-arginine) in serum samples from PC patients might provide a sensitive, blood-borne diagnostic signature for the presence of PC or its precursor lesions.
胰腺癌（PC）是癌症死亡的第四大主要原因，因为其在早期阶段的临床症状较为隐匿。因此，迫切需要发现特定的血清代谢物作为潜在的生物标志物，以将胰腺癌与良性疾病（BD）区分开来。
为了全面分析来自 14 名 PC 患者、10 名 BD 患者和 10 名健康个体（正常对照，NC）的血清代谢物，我们分别采用反相液相色谱（RPLC）和亲水相互作用液相色谱（HILIC）对代谢物进行分离。数据分别在分别在负离子（ESI-）和正离子（ESI+）模式下的高分辨率四极杆飞行时间质谱仪上采集。通过单变量（Student's t 检验）和多变量（正交偏最小二乘判别分析（OPLS-DA））统计分别选择差异代谢物。进一步利用序贯窗口采集所有理论谱（SWATH）分析对发现阶段中发现的代谢物进行验证。通过受试者工作特征（ROC）曲线分析评估 8 种代谢物的预测临床有用性。
共鉴定并相对定量了 8 种代谢物，包括牛磺胆酸、甘氨胆酸、甘氨鹅脱氧胆酸、L-谷氨酰胺、谷氨酸、L-苯丙氨酸、L-色氨酸和 L-精氨酸，这些代谢物可用于区分 PC、BD 和 NC。这 8 种代谢物及其组合可将 PC 与 BD 和 NC 区分开来，具有良好的曲线下面积（AUC）值、灵敏度和特异性。
胆汁酸（尤其是牛磺胆酸）可作为 PC 诊断的潜在生物标志物。PC 患者血清样本中的其他氨基酸（如 L-谷氨酰胺、谷氨酸、L-苯丙氨酸、L-色氨酸和 L-精氨酸）可能为 PC 或其前体病变的存在提供敏感的、血液来源的诊断特征。
