Potential prognostic biomarkers of pancreatic cancer.

Potential prognostic biomarkers of pancreatic cancer.
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DOI:
10.1097/mpa.0b013e3182a6867e
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发表时间:
2014-01
期刊:
影响因子:
2.9
通讯作者:
Yeung AT
Yeung AT
中科院分区:
医学4区
文献类型:
--
作者:
Chen KT;Kim PD;Jones KA;Devarajan K;Patel BB;Hoffman JP;Ehya H;Huang M;Watson JC;Tokar JL;Yeung AT

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我们评估了胰腺主导管液是否可以提供具有预后价值的蛋白质生物标志物。质谱蛋白质组学应用于肿瘤手术切除时收集的少至20微升的液体。27例患者的生物标志物蛋白与临床结果相关。13例患者患有胰腺导管腺癌(PDAC),4例患有IPMN伴原位腺癌,5例患有壶腹腺癌,2例患有IPMNs,3例患有良性疾病。在病理II期或更高的PDAC中,S100A8或S100A9蛋白的中度或高度表达与5.8个月的中位疾病无复发生存期相关,而低表达患者为17.3个月(p=0.002)。中位总生存期为12.6个月,中度至高度与低S100A8和A9表达的患者为27个月(p=0.02)。该分析表明胰腺癌的不同蛋白质组特征。在我们的研究中,发现导管液中S100A8或A9水平升高、几乎不存在胰酶和高水平粘蛋白的患者预后显著较差。虽然需要进一步验证来证实这些发现,但胰腺导管液分析是鉴定感兴趣的生物标志物的有希望的工具。
We evaluated whether pancreatic main duct fluid can provide protein biomarkers with prognostic value. Mass spectrometry proteomics was applied to as little as 20 microliters of fluid collected at the time of tumor surgical resection. Biomarker proteins identified for 27 patients were correlated with clinical outcomes. Thirteen patients had pancreatic ductal adenocarcinomas (PDAC), 4 had IPMN with in situ adenocarcinoma, 5 had ampullary adenocarcinomas, 2 had IPMNs and 3 had benign diseases. In pathologic stage II or higher PDAC, moderate or high expression of S100A8 or S100A9 proteins was associated with a median disease recurrence-free survival of 5.8 months compared to 17.3 months in patients with low expression (p=0.002). Median overall survival was 12.6 versus 27 months for patients with moderate to high versus low S100A8 and A9 expression (p=0.02). This analysis suggests distinct proteomic signatures for pancreatic cancer. Patients in our study with elevated levels of S100A8 or A9 in the ductal fluid, a near absence of pancreatic enzymes, and high levels of mucins, were found to have significantly worse prognosis. Although further validation is needed to corroborate these findings, analysis of pancreatic ductal fluid is a promising tool for identifying biomarkers of interest.