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基质辅助激光解吸电离飞行时间质谱分析在卵巢癌血清蛋白质组学模式的发现与鉴定中的应用

MALDI-TOF-MS analysis in discovery and identification of serum proteomic patterns of ovarian cancer.

作者信息

Swiatly Agata, Horala Agnieszka, Hajduk Joanna, Matysiak Jan, Nowak-Markwitz Ewa, Kokot Zenon J

机构信息

Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, ul. Grunwaldzka 6, 60-780, Poznań, Poland.

Gynecologic Oncology Department, Poznan University of Medical Sciences, ul. Polna 33, 60-535, Poznań, Poland.

出版信息

BMC Cancer. 2017 Jul 6;17(1):472. doi: 10.1186/s12885-017-3467-2.

Abstract

BACKGROUND

Due to high mortality and lack of efficient screening, new tools for ovarian cancer (OC) diagnosis are urgently needed. To broaden the knowledge on the pathological processes that occur during ovarian cancer tumorigenesis, protein-peptide profiling was proposed.

METHODS

Serum proteomic patterns in samples from OC patients were obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF). Eighty nine serum samples (44 ovarian cancer and 45 healthy controls) were pretreated using solid-phase extraction method. Next, a classification model with the most discriminative factors was identified using chemometric algorithms. Finally, the results were verified by external validation on an independent test set of samples.

RESULTS

Main outcome of this study was an identification of potential OC biomarkers by applying liquid chromatography coupled with tandem mass spectrometry. Application of this novel strategy enabled the identification of four potential OC serum biomarkers (complement C3, kininogen-1, inter-alpha-trypsin inhibitor heavy chain H4, and transthyretin). The role of these proteins was discussed in relation to OC pathomechanism.

CONCLUSIONS

The study results may contribute to the development of clinically useful multi-component diagnostic tools in OC. In addition, identifying a novel panel of discriminative proteins could provide a new insight into complex signaling and functional networks associated with this multifactorial disease.

摘要

背景

由于卵巢癌(OC)死亡率高且缺乏有效的筛查手段,迫切需要新的卵巢癌诊断工具。为了拓宽对卵巢癌肿瘤发生过程中病理过程的认识,提出了蛋白质-肽谱分析方法。

方法

使用基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF)获得卵巢癌患者样本中的血清蛋白质组模式。89份血清样本(44份卵巢癌样本和45份健康对照样本)采用固相萃取法进行预处理。接下来,使用化学计量学算法确定具有最显著区分因素的分类模型。最后,通过对独立样本测试集进行外部验证来验证结果。

结果

本研究的主要成果是通过液相色谱-串联质谱联用技术鉴定出潜在的卵巢癌生物标志物。应用这种新策略能够鉴定出四种潜在的卵巢癌血清生物标志物(补体C3、激肽原-1、α-胰蛋白酶抑制剂重链H4和转甲状腺素蛋白)。讨论了这些蛋白质在卵巢癌发病机制中的作用。

结论

研究结果可能有助于开发临床上有用的卵巢癌多组分诊断工具。此外,鉴定一组新的具有区分性的蛋白质可以为与这种多因素疾病相关的复杂信号传导和功能网络提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35a/5501370/dd7fb66c4d1d/12885_2017_3467_Fig1_HTML.jpg

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