Signal Transduction and Targeted Therapy ( IF 40.8 ) Pub Date : 2023-10-18 , DOI: 10.1038/s41392-023-01645-8
Ming Cui 1 , Ya Hu 1 , Zejian Zhang 2 , Tianqi Chen 2 , Menghua Dai 1 , Qiang Xu 1 , Junchao Guo 1 , Taiping Zhang 1 , Quan Liao 1 , Jun Yu 3, 4 , Yupei Zhao 1
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Pancreatic cystic neoplasms (PCNs) are recognized as precursor lesions of pancreatic cancer, with a marked increase in prevalence. Early detection of malignant PCNs is crucial for improving prognosis; however, current diagnostic methods are insufficient for accurately identifying malignant PCNs. Here, we utilized mass spectrometry (MS)-based glycosite- and glycoform-specific glycoproteomics, combined with proteomics, to explore potential cyst fluid diagnostic biomarkers for PCN. The glycoproteomic and proteomic landscape of pancreatic cyst fluid samples from PCN patients was comprehensively investigated, and its characteristics during the malignant transformation of PCN were analyzed. Under the criteria of screening specific cyst fluid biomarkers for the diagnosis of PCN, a group of cyst fluid glycoprotein biomarkers was identified. Through parallel reaction monitoring (PRM)-based targeted glycoproteomic analysis, we validated these chosen glycoprotein biomarkers in a second cohort, ultimately confirming N-glycosylated PHKB (Asn-935, H5N2F0S0; Asn-935, H4N4F0S0; Asn-935, H5N4F0S0), CEACAM5 (Asn-197, H5N4F0S0) and ATP6V0A4 (Asn-367, H6N4F0S0) as promising diagnostic biomarkers for distinguishing malignant PCNs. These glycoprotein biomarkers exhibited robust performance, with an area under the curve ranging from 0.771 to 0.948. In conclusion, we successfully established and conducted MS-based glycoproteomic analysis to identify novel cyst fluid glycoprotein biomarkers for PCN. These findings hold significant clinical implications, providing valuable insights for PCN decision-making, and potentially offering therapeutic targets for PCN treatment.
中文翻译:
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囊液糖蛋白准确区分胰腺囊性肿瘤的恶性肿瘤
胰腺囊性肿瘤(PCN)被认为是胰腺癌的前驱病变,其患病率显着增加。早期发现恶性 PCN 对于改善预后至关重要;然而,目前的诊断方法不足以准确识别恶性 PCN。在这里,我们利用基于质谱(MS)的糖位点和糖型特异性糖蛋白质组学,结合蛋白质组学,探索潜在的 PCN 囊液诊断生物标志物。全面研究PCN患者胰腺囊肿液样本的糖蛋白组和蛋白质组图谱,并分析其在PCN恶变过程中的特征。根据筛选诊断 PCN 的特定囊液生物标志物的标准,鉴定了一组囊液糖蛋白生物标志物。通过基于平行反应监测(PRM)的靶向糖蛋白组分析,我们在第二组中验证了这些选定的糖蛋白生物标志物,最终确认了 N-糖基化 PHKB(Asn-935,H5N2F0S0;Asn-935,H4N4F0S0;Asn-935,H5N4F0S0), CEACAM5(Asn-197、H5N4F0S0)和 ATP6V0A4(Asn-367、H6N4F0S0)作为区分恶性 PCN 的有前途的诊断生物标志物。这些糖蛋白生物标志物表现出稳健的性能,曲线下面积范围为 0.771 至 0.948。总之,我们成功建立并进行了基于 MS 的糖蛋白质组分析,以确定 PCN 的新型囊液糖蛋白生物标志物。这些发现具有重要的临床意义,为 PCN 决策提供了宝贵的见解,并有可能为 PCN 治疗提供治疗靶点。