Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors.
Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors.
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DOI：
10.1159/000161012
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Maitra A
中科院分区：
文献类型：
--
作者：
Cheung W;Darfler MM;Alvarez H;Hood BL;Conrads TP;Habbe N;Krizman DB;Mollenhauer J;Feldmann G;Maitra A
胰腺癌是一种几乎一致致命的疾病，早期发现是提高生存率的关键决定因素。胰腺癌的各种非侵入性前驱病变已被确定，这提供了一个独特的机会，在浸润性癌症发病前进行干预。在前体病变中的生物标志物发现受到新鲜标本的现成可用性和适合于大规模筛选的蛋白质的有限产量的阻碍。我们利用Liquid Tissue®（一种从存档福尔马林固定材料中提取蛋白质的新技术）和质谱法对导管内乳头状粘液性肿瘤（IPMN）进行了全面的蛋白质组学分析。由38个IPMN组成的组织微阵列用于验证候选蛋白。IPMN Liquid Tissue裂解物的蛋白质组学分析鉴定了1，534种肽，对应于523种独特蛋白质。鉴定了先前报道在胰腺癌中上调的25种蛋白质的子集。对其中两种（在恶性脑肿瘤中缺失1（DMBT 1）和组织转谷氨酰胺酶2（TGM 2））的免疫组织化学分析证实了它们在IPMNs中的过表达。使用Liquid Tissue工作流程的全局蛋白质组学分析是在有限的档案材料中发现无偏倚生物标志物的可行方法，特别适用于癌症的前驱病变。
Pancreatic cancer is an almost uniformly fatal disease, and early detection is a critical determinant of improved survival. A variety of noninvasive precursor lesions of pancreatic adenocarcinoma have been identified, which provide a unique opportunity for intervention prior to onset of invasive cancer. Biomarker discovery in precursor lesions has been hampered by the ready availability of fresh specimens, and limited yields of proteins suitable for large scale screening. We utilized Liquid Tissue®, a novel technique for protein extraction from archival formalin-fixed material, and mass spectrometry to conduct a global proteomic analysis of an intraductal papillary mucinous neoplasm (IPMN). Tissue microarrays comprised of 38 IPMNs were used for validation of candidate proteins. The proteomic analysis of the IPMN Liquid Tissue lysate resulted in identification of 1,534 peptides corresponding to 523 unique proteins. A subset of 25 proteins was identified that had previously been reported as upregulated in pancreatic cancer. Immunohistochemical analysis for two of these, deleted in malignant brain tumors 1 (DMBT1) and tissue transglutaminase 2 (TGM2), confirmed their overexpression in IPMNs. Global proteomics analysis using the Liquid Tissue workflow is a feasible approach for unbiased biomarker discovery in limited archival material, particularly applicable to precursor lesions of cancer.
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影响因子：
5
作者：
Crockett, DK;Lin, ZS;Elenitoba-Johnson, KSJ
通讯作者：
Elenitoba-Johnson, KSJ
影响因子：
7
作者：
Hood, BL;Darfler, MM;Krizman, DB
通讯作者：
Krizman, DB
影响因子：
8
作者：
Crnogorac-Jurcevic, T;Efthimiou, E;Lemoine, NR
通讯作者：
Lemoine, NR
影响因子：
3.5
作者：
Furukawa, T;Klöppel, G;Yonezawa, S
通讯作者：
Yonezawa, S
影响因子：
3.6
作者：
Hustinx, SR;Cao, DF;Hruban, RH
通讯作者：
Hruban, RH