关键词: 血清多肽组学, 基质辅助激光解吸电离飞行时间质谱, 胰腺癌, 慢性胰腺炎

Abstract:

Objective To investigate the role of serum peptidomics based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry（MALDI-TOF MS） in the differential diagnosis of benign and malignant pancreatic diseases. Methods A total of 176 patients with pancreatic ductal adenocarcinoma（PDAC） and 148 patients with chronic pancreatitis（CP） were enrolled and randomly classified into training set（122 cases of PDAC，103 cases of CP） and validation set（54 cases of PDAC，45 cases of CP） at a ratio of 7 to 3. Serum peptides were extracted by weak positive ion exchange method combined with magnetic bead adsorption，and peptide profiles were determined by MALDI-TOF MS. In the training set，binary Logistic regression analysis was used to establish a differential diagnosis model for distinguishing PDAC from CP based on differentially expressed peptides，and in the validation set，the model was verified. The amino acid sequences of differentially expressed peptides were determined by nano-liquid chromatography-electrospray ionization-tandem mass spectrometry（nano-LC/ESI-MS/MS），and the proteins to which they belonged to were identified. Receiver operating characteristic（ROC） curve was used to evaluate the efficacy of the differential diagnosis model in distinguishing PDAC from CP，which was compared with the differential diagnosis efficacy of serum carbohydrate antigen 19-9（CA19-9）. Results A total of 20 peptides were found to be different between PDAC and CP patients. The area under curve（AUC） of the differential diagnosis model established based on these 20 peptides was 0.988，the optimal cut-off value was 0.469，the sensitivity was 94.26%，and the specificity was 97.09%. In the validation set，the sensitivity of the model was 94.44%，and the specificity was 97.78%. The performance of differential diagnosis model was better than that of serum CA19-9（the sensitivity of 67.90% and the specificity of 91.30%）. The AUC of the differential diagnosis model combined with CA19-9 to distinguish PDAC and CP was 0.996，the sensitivity was 97.60%，and the specificity was 100.00%. The proteins to which the 3 peptides belonged to were successfully identified by nano-LC/ESI-MS/MS，m/z 1 758 was the fragment of zyxin，and m/z 4 053 and m/z 5 351 were both the fragments of fibrinogen. Conclusions A model for the differential diagnosis of PDAC and CP has been established based on serum peptidomics，which can distinguish PDAC from CP and malignant pancreatic diseases accurately，and it provides an idea for the further development of a non-invasive cancer diagnosis method.

Key words: Serum peptidomics, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, Pancreatic cancer, Chronic pancreatitis