Integrated proteomics and phosphoproteomics reveal perturbed regulative pathways in pancreatic ductal adenocarcinoma,Molecular Omics

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Integrated proteomics and phosphoproteomics reveal perturbed regulative pathways in pancreatic ductal adenocarcinoma
Molecular Omics ( IF 3.0 ) Pub Date : 2020-12-23 , DOI: 10.1039/d0mo00125b
Lianyuan Tao ₁ , Lijun Zhong ₂ , Yang Li ₃ , Deyu Li ₄ , Dianrong Xiu ₅ , Juntuo Zhou ₆

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Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to its inefficient diagnosis, rapid progress, and tenacious drug resistance. Here, we aimed to analyze the expressive patterns of proteins and phosphorylation in PDAC tissue samples and compare them to normal pancreatic tissue to investigate the underlying mechanisms and to reveal potential protein targets for diagnosis and drug development. Liquid chromatography coupled to mass spectrometry (LC-MS) based proteomics and phosphoproteomics analyses were performed using 20 pairs of patient-derived PDAC tissue and normal pancreatic tissue samples. Protein identification and quantification were conducted using MaxQuant software. Bioinformatics analysis was used to retrieve PDAC-relevant pathways and gene ontology (GO) terms. 4985 proteins and 3643 phosphoproteins were identified with high confidence; of these, 322 proteins and 235 phosphoproteins were dysregulated in PDAC. Several pathways, including several extracellular matrix-related pathways, were found to be strongly associated with PDAC. Further, the expression levels of filamin A (FLNA), integrin alpha-V (ITGAV), thymidine phosphorylase (TYMP), medium-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADM), short-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADS), and acetyl-CoA acetyltransferase, mitochondrial (ACAT1) were examined through western blot and immunohistochemistry analysis, and the results confirmed the validity of the proteomics analysis results. These findings provide comprehensive insight into the dysregulated regulative networks in PDAC tissue samples at the protein and phosphorylation levels, and they provide clues for further pathological studies and drug-target development.

中文翻译：

综合蛋白质组学和磷酸化蛋白质组学揭示胰腺导管腺癌中紊乱的调节通路

胰腺导管腺癌 (PDAC) 的预后不佳，主要是由于其诊断效率低、进展迅速和耐药性顽强。在这里，我们旨在分析 PDAC 组织样本中蛋白质和磷酸化的表达模式，并将它们与正常胰腺组织进行比较，以研究潜在的机制并揭示用于诊断和药物开发的潜在蛋白质靶标。使用 20 对源自患者的 PDAC 组织和正常胰腺组织样本，进行了基于蛋白质组学和磷酸化蛋白质组学的液相色谱与质谱联用 (LC-MS) 分析。使用 MaxQuant 软件进行蛋白质鉴定和定量。生物信息学分析用于检索 PDAC 相关通路和基因本体 (GO) 术语。4985 种蛋白质和 3643 种磷蛋白被高可信度鉴定；其中，322 种蛋白质和 235 种磷蛋白在 PDAC 中失调。发现多种途径，包括多种细胞外基质相关途径，与 PDAC 密切相关。此外，细丝蛋白 A (FLNA)、整合素 α-V (ITGAV)、胸苷磷酸化酶 (TYMP)、中链特异性酰基辅酶 A 脱氢酶、线粒体 (ACADM)、短链特异性酰基辅酶 A 脱氢酶、线粒体的表达水平(ACADS) 和乙酰辅酶 A 乙酰转移酶，线粒体 (ACAT1) 通过蛋白质印迹和免疫组织化学分析进行检查，结果证实了蛋白质组学分析结果的有效性。

更新日期：2020-12-23

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