Background

Pancreatic ductal adenocarcinoma (PDAC) has the lowest survival rate of all major cancers. Surgery is the only curative intent therapy, but the majority of patients experience disease relapse. Thus, patients who do not benefit from highly morbid surgical resection needs to be identified and offered palliative chemotherapy instead. In this pilot study, we aimed to identify differentially regulated proteins in plasma and plasma derived microparticles from PDAC patients with poor and good prognosis.

Methods

Plasma and plasma derived microparticle samples were obtained before surgical resection from PDAC patients. Sequential Windowed Acquisition of all Theoretical fragment ion spectra – Mass Spectrometry (SWATH-MS) proteomic analysis was performed to identify and quantify proteins in these samples. Statistical analysis was performed to identify biomarkers for poor prognosis.

Results

A total of 482 and 1024 proteins were identified from plasma and microparticle samples, respectively, by SWATH-MS analysis. Statistical analysis of the data further identified nine and six differentially (log₂ratio > 1, p < .05) expressed proteins in plasma and microparticles, respectively. Protein tyrosine phosphatases, PTPRM and PTPRB, were decreased in plasma of patients with poor PDAC prognosis, while proteasomal subunit PSMD11 was increased in microparticles of patients with poor prognosis.

Conclusion and general significance

A novel blood-based biomarker signature for PDAC prognosis was identified.

中文翻译：

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PSMD11，PTPRM和PTPRB是胰腺癌进展的新型生物标志物。

背景

胰腺导管腺癌（PDAC）在所有主要癌症中的存活率最低。外科手术是唯一的治疗方法，但是大多数患者会复发。因此，需要识别出不能从高病态手术切除中受益的患者，而应采用姑息化疗。在这项初步研究中，我们旨在鉴定预后不良和良好的PDAC患者血浆和血浆来源的微粒中差异调节的蛋白质。

方法

在手术切除之前，从PDAC患者中获取血浆和血浆来源的微粒样品。对所有理论碎片离子谱图进行顺序窗口采集–进行了质谱（SWATH-MS）蛋白质组学分析，以鉴定和定量这些样品中的蛋白质。进行统计分析以鉴定不良预后的生物标志物。

结果

通过SWATH-MS分析，分别从血浆和微粒样品中鉴定出总共482和1024种蛋白质。数据的统计分析进一步确定了血浆和微粒中分别有9种和6种差异表达（log ₂比> 1，p <.05）。PDAC预后不良的患者血浆中的蛋白质酪氨酸磷酸酶PTPRM和PTPRB降低，预后不良的患者微粒中的蛋白酶体亚基PSMD11升高。

结论与一般意义

确定了一种新颖的基于血液的生物标志物，用于PDAC预后。