Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients.
Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients.
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DOI：
10.1186/1471-2407-8-241
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发表时间：
2008-08-16
期刊：
影响因子：
3.8
通讯作者：
Han, Jin-Xiang
中科院分区：
文献类型：
--
作者：
Tian, Mei;Cui, Ya-Zhou;Song, Guan-Hua;Zong, Mei-Juan;Zhou, Xiao-Yan;Chen, Yu;Han, Jin-Xiang
目前迫切需要发现更敏感和特异的生物标志物，以提高胰腺导管腺癌（PDAC）的早期诊断和筛查高危患者。胰液是PDAC生物标志物发现的理想标本，因为它是胰腺癌细胞释放的蛋白质的异常丰富的来源。为了从胰液中鉴定PDAC的新的潜在生物标志物，我们进行了差异凝胶电泳（DIGE）和串联质谱（MS/MS）以比较来自9名PDAC患者和9名无癌症对照的胰液谱。在所鉴定的差异表达蛋白中，选择胰腺癌汁液中的三种上调蛋白，基质金属蛋白酶-9（MMP-9）、癌基因DJ 1（DJ-1）和α-1B-糖蛋白前体（A1 BG），通过Western印迹和免疫组织化学进行验证。采用酶联免疫吸附法（ELISA）检测血清MMP-9水平。与无癌对照组相比，癌性胰液中有14种蛋白质表达上调，10种蛋白质表达下调。Western blot证实癌性胰液中MMP-9、DJ-1和A1 BG表达增加。免疫组化显示MMP-9、DJ-1和A1 BG在胰腺癌组织中的阳性表达率分别为82.4%、72.5%和86.3%，显著高于正常胰腺组织。DJ-1的上调与更好的分化相关（p < 0.05）。PDAC组血清MMP-9水平（255.14 ng/ml）显著高于慢性胰腺炎组（210.22 ng/ml，p = 0.009）和健康对照组（203.77 ng/ml，p = 0.027）。目前的蛋白质组分析显示，MMP-9，DJ-1和A1 BG蛋白在PDAC的胰液中升高，这表明它们在PDAC诊断和筛查中的进一步用途。这是A1 BG首次被确定为胰腺癌相关样本中的潜在生物标志物。血清MMP-9的检测对PDAC的诊断有一定的临床意义。
There is an urgent need to discover more sensitive and specific biomarkers to improve early diagnosis and screen high-risk patients for pancreatic ductal adenocarcinoma (PDAC). Pancreatic juice is an ideal specimen for PDAC biomarkers discovery, because it is an exceptionally rich source of proteins released from pancreatic cancer cells. To identify novel potential biomarkers for PDAC from pancreatic juice, we carried out difference gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS) to compare the pancreatic juice profiling from 9 PDAC patients and 9 cancer-free controls. Of the identified differently expressed proteins, three up-regulated proteins in pancreatic cancer juice, matrix metalloproteinase-9 (MMP-9), oncogene DJ1 (DJ-1) and alpha-1B-glycoprotein precursor (A1BG), were selected for validation by Western blot and immunohistochemistry. Serum MMP-9 levels were also detected by enzyme linked immunosorbent assay (ELISA). Fourteen proteins were up-regulated and ten proteins were down-regulated in cancerous pancreatic juice compared with cancer-free controls. Increased MMP-9, DJ-1 and A1BG expression in cancerous pancreatic juice were confirmed by Western blot. Immunohistochemical study showed MMP-9, DJ-1 and A1BG positively expressed in 82.4%, 72.5% and 86.3% of pancreatic cancer tissues, significantly higher than that in normal pancreas tissues. Up-regulation of DJ-1 was associated with better differentiation (p < 0.05). Serum MMP-9 levels were significantly higher in PDAC (255.14 ng/ml) than those in chronic pancreatitis (210.22 ng/ml, p = 0.009) and healthy control (203.77 ng/ml, p = 0.027). The present proteome analysis revealed MMP-9, DJ-1 and A1BG proteins as elevated in pancreatic juice from PDAC, which suggest their further utility in PDAC diagnosis and screening. This is the first time A1BG was identified as a potential biomarker in pancreatic cancer associated samples. The measurement of serum MMP-9 might be clinically useful for PDAC diagnosis.
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影响因子：
2.9
作者：
Chen, Ru;Pan, Sheng;Brentnall, Teresa A.
通讯作者：
Brentnall, Teresa A.
影响因子：
9.3
作者：
Melle, Christian;Ernst, Guenther;von Eggeling, Ferdinand
通讯作者：
von Eggeling, Ferdinand
影响因子：
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作者：
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DOI：
10.1016/s1385-299x(01)00123-4
发表时间：
2002-02-01
期刊：
BRAIN RESEARCH PROTOCOLS
影响因子：
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作者：
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通讯作者：
Rampin, O
影响因子：
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作者：
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通讯作者：
Goodison, Steve