Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms.
Glycosylation variants of mucins and CEACAMs as candidate biomarkers for the diagnosis of pancreatic cystic neoplasms.
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DOI：
10.1097/sla.0b013e3181d7738d
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发表时间：
2010-05
影响因子：
9
通讯作者：
Simeone DM
中科院分区：
文献类型：
--
作者：
Haab BB;Porter A;Yue T;Li L;Scheiman J;Anderson MA;Barnes D;Schmidt CM;Feng Z;Simeone DM
由于高分辨率腹部成像的广泛应用，胰腺囊性病变越来越多地被发现。由于某些囊肿类型是侵袭性癌症的先兆，这种情况提供了在恶性进展之前进行干预的机会。由于难以明确区分无恶性潜能的囊性病变和有恶性潜能的囊性病变，这一战略的有效实施受到了阻碍。在这里，我们探讨了囊肿液样本中特定蛋白质的糖基化变异是否可以作为生物标志物来帮助诊断。我们利用一种新的抗体-凝集素三明治微阵列方法来测量囊肿液样本中MUC1、MUC5AC、MUC16、CEA和其他与胰腺肿瘤有关的蛋白质的表达和糖基化。53例囊肿液样本来自于粘液性囊性肿瘤（MCN, n = 17）、导管内乳头状粘液性肿瘤（IPMN, n = 15）、浆液性囊腺瘤（SC, n = 12）或假性囊肿（PC, n = 9），并在手术切除时得到组织学诊断。使用凝集素小麦胚芽凝集素检测MUC5AC上的聚糖变体，区分产生黏素的囊性肿瘤（MCNs + ipmn）和良性囊性病变（SC + PC），灵敏度为78%，特异性为80%，当与囊肿液ca19 -9联合使用时，灵敏度为87%，特异性为86%。这些生物标志物的表现优于囊肿液CEA（37%/80%的敏感性/特异性）。这些结果证明了聚糖变体在发现生物标志物方面的价值，并表明这些生物标志物可以大大提高胰腺囊性肿瘤鉴别的准确性。需要进行验证研究来确定这些标记物的临床价值。
Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of high resolution abdominal imaging. Since certain cyst types are precursors to invasive cancer, this situation presents an opportunity to intervene prior to malignant progression. Effective implementation of that strategy has been hampered by difficulties in clearly distinguishing cystic lesions with no malignant potential from those with malignant potential. Here we explored whether glycosylation variants on specific proteins in cyst fluid samples could serve as biomarkers to aid in this diagnosis. We utilized a novel antibody-lectin sandwich microarray method to measure the protein expression and glycosylation of MUC1, MUC5AC, MUC16, CEA, and other proteins implicated in pancreatic neoplasia in cyst fluid samples. Fifty-three cyst fluid samples were obtained from patients with mucinous cystic neoplasms (MCN, n = 17), intraductal papillary mucinous neoplasms (IPMN, n = 15), serous cystadenomas (SC, n = 12), or pseudocysts (PC, n = 9), with confirmation of histologic diagnosis at surgical resection. The detection of a glycan variant on MUC5AC using the lectin wheat-germ agglutinin discriminated mucin-producing cystic tumors (MCNs + IPMNs) from benign cystic lesions (SC + PC) with a 78% sensitivity at 80% specificity, and when used in combination with cyst fluid CA 19-9 gave a sensitivity of 87% at 86% specificity. These biomarkers performed better than cyst fluid CEA (37%/80% sensitivity/specificity). These results demonstrate the value of glycan variants for biomarker discovery and suggest that these biomarkers could greatly enhance the accuracy of differentiating pancreatic cystic tumors. Validation studies will be required to determine the clinical value of these markers.