Proteomic mucin profiling for the identification of cystic precursors of pancreatic cancer.
Proteomic mucin profiling for the identification of cystic precursors of pancreatic cancer.
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DOI：
10.1093/jnci/djt439
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发表时间：
2014-02
期刊：
影响因子：
--
通讯作者：
Sadik R
中科院分区：
文献类型：
--
作者：
Jabbar KS;Verbeke C;Hyltander AG;Sjövall H;Hansson GC;Sadik R
胰腺囊性病变（PCLs）是越来越常见的放射偶发瘤，有相当比例代表胰腺癌的前兆。需要更好的诊断工具，以便患者从这一发展中受益。为了评估囊肿液粘蛋白表达是否可以预测pcl的恶性潜能和/或转化，我们设计了一种蛋白质组学方法，并对2007年5月至2008年11月（发现队列）和2008年12月至2012年10月（验证队列）在我们三级中心进行内镜超声引导下囊性病变穿刺的连续患者进行前瞻性评估。常规分析细胞学和囊液癌胚抗原（CEA，癌前> 192ng/mL，恶性> 1000ng/mL），并对样品进行进一步处理：一维凝胶电泳、高质区切除、色氨酸消化、纳米液相色谱-串联质谱，通过Mascot软件和内部黏液蛋白数据库进行肽鉴定。所有诊断评估均对蛋白质组学结果不知情。需要组织学来确认是否存在恶性转化。所有统计检验均为双侧检验。蛋白组学粘蛋白谱在鉴别37例（79例中，46.8%）有恶性潜在病变（即癌前或恶性肿瘤）时，比细胞学（71.4%,95% CI = 59.8%至80.9%,P < 0.001）和囊肿液CEA （78.0%, 95% CI = 65.0%至87.3%,P < 0.001）具有统计学上的显著准确性（97.5%，95%置信区间[CI] = 90.3%至99.6%）。在发现组（n = 29）和验证组（n = 50）之间，蛋白质组学的准确性几乎相同（96.6% vs 98.0%）。此外，黏液蛋白谱预测了恶性转化，在29个（发现组：9个，验证组：20个）病变中有16个（发现组：9个，验证组：20个），准确率为89.7% (95% CI = 71.5%至97.3%)（验证组仅为95.0%;95% CI = 73.1%至99.7%）。这明显超过细胞学（51.7%;95% CI = 32.9% ~ 70.1%; P = 0.003）和CEA （57.1%; 95% CI = 34.4% ~ 77.4%; P = 0.02）的相应结果。蛋白质组学囊肿液粘蛋白谱可有效区分良性、癌前和恶性pcl。因此，它可以改善胰腺癌的预防和减少不必要的胰腺手术的发病率负担。
Pancreatic cystic lesions (PCLs) are increasingly frequent radiological incidentalomas, with a considerable proportion representing precursors of pancreatic cancer. Better diagnostic tools are required for patients to benefit from this development. To evaluate whether cyst fluid mucin expression could predict malignant potential and/or transformation in PCLs, a proteomic method was devised and prospectively evaluated in consecutive patients referred to our tertiary center for endoscopic ultrasound-guided aspiration of cystic lesions from May 2007 through November 2008 (discovery cohort) and from December 2008 through October 2012 (validation cohort). Cytology and cyst fluid carcinoembryonic antigen (CEA; premalignancy > 192ng/mL, malignancy > 1000ng/mL) were routinely analyzed, and samples were further processed as follows: one-dimensional gel electrophoresis, excision of high-mass areas, tryptic digestion and nano-liquid chromatography–tandem mass spectrometry, with peptide identification by Mascot software and an in-house mucin database. All diagnostic evaluations were blinded to proteomics results. Histology was required to confirm the presence/absence of malignant transformation. All statistical tests were two-sided. Proteomic mucin profiling proved statistically significantly more accurate (97.5%; 95% confidence interval [CI] = 90.3% to 99.6%) than cytology (71.4%; 95% CI = 59.8% to 80.9%; P < .001) and cyst fluid CEA (78.0%; 95% CI = 65.0% to 87.3%; P < .001) in identifying the 37 (out of 79; 46.8%) lesions with malignant potential (ie, premalignant or malignant tumors). The accuracy of proteomics was nearly identical (96.6% vs 98.0%) between the discovery (n = 29) and validation (n = 50) cohorts. Furthermore, mucin profiling predicted malignant transformation, present in 16 out of 29 (discovery cohort: 9, validation cohort: 20) lesions with available histology, with 89.7% accuracy (95% CI = 71.5% to 97.3%) (for the validation cohort only: 95.0%; 95% CI = 73.1% to 99.7%). This markedly exceeded corresponding results for cytology (51.7%; 95% CI = 32.9% to 70.1%; P = .003) and CEA (57.1%; 95% CI = 34.4% to 77.4%; P = .02). Proteomic cyst fluid mucin profiling robustly discriminates benign, premalignant, and malignant PCLs. Consequently, it may improve pancreatic cancer prevention and reduce the morbidity burden of unwarranted pancreatic surgery.
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影响因子：
3.7
作者：
Cho CS;Russ AJ;Loeffler AG;Rettammel RJ;Oudheusden G;Winslow ER;Weber SM
通讯作者：
Weber SM
影响因子：
7.5
作者：
Adsay, NV;Merati, K;Klimstra, DS
通讯作者：
Klimstra, DS
影响因子：
7.7
作者：
Khalid, Asif;Zahid, Maliha;McGrath, Kevin M.
通讯作者：
McGrath, Kevin M.
影响因子：
48
作者：
Gillette, Michael A.;Carr, Steven A.
通讯作者：
Carr, Steven A.
影响因子：
9.3
作者：
de Jong, K.;Poley, J-W;Fockens, P.
通讯作者：
Fockens, P.