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外泌体蛋白筛选及其作为胰腺癌诊断和预后生物标志物的潜力。

Screening of Exosome-Derived Proteins and Their Potential as Biomarkers in Diagnostic and Prognostic for Pancreatic Cancer.

机构信息

Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81350-010, Brazil.

Mass Spectrometry Facility RPT02H, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba 81350-010, Brazil.

出版信息

Int J Mol Sci. 2023 Aug 9;24(16):12604. doi: 10.3390/ijms241612604.

Abstract

In the oncological area, pancreatic cancer is one of the most lethal diseases, with 5-year survival rising just 10% in high-development countries. This disease is genetically characterized by as a driven mutation followed by , , and -associated mutations. In clinical aspects, pancreatic cancer presents unspecific clinical symptoms with the absence of screening and early plasmatic biomarker, being that CA19-9 is the unique plasmatic biomarker having specificity and sensitivity limitations. We analyzed the plasmatic exosome proteomic profile of 23 patients with pancreatic cancer and 10 healthy controls by using Nanoscale liquid chromatography coupled to tandem mass spectrometry (NanoLC-MS/MS). The pancreatic cancer patients were subdivided into IPMN and PDAC. Our findings show 33, 34, and 7 differentially expressed proteins when comparing the IPMN vs. control, PDAC-No treatment vs. control, and PDAC-No treatment vs. IPMN groups, highlighting proteins of the complement system and coagulation, such as C3, APOB, and SERPINA. Additionally, PDAC with no treatment showed 11 differentially expressed proteins when compared to Folfirinox neoadjuvant therapy or Gemcitabine adjuvant therapy. So here, we found plasmatic exosome-derived differentially expressed proteins among cancer patients (IPMN, PDAC) when comparing with healthy controls, which could represent alternative biomarkers for diagnostic and prognostic evaluation, supporting further scientific and clinical studies on pancreatic cancer.

摘要

在肿瘤学领域,胰腺癌是最致命的疾病之一,高发达国家的 5 年生存率仅提高了 10%。这种疾病在遗传上的特征是驱动突变,随后是 KRAS、TP53 和 CDKN2A 相关突变。在临床方面,胰腺癌表现出非特异性的临床症状,缺乏筛查和早期血浆生物标志物,而 CA19-9 是唯一具有特异性和敏感性限制的血浆生物标志物。我们通过使用纳升液相色谱-串联质谱(NanoLC-MS/MS)分析了 23 名胰腺癌患者和 10 名健康对照者的血浆外泌体蛋白质组图谱。将胰腺癌患者分为 IPMN 和 PDAC 两组。我们的研究结果显示,当比较 IPMN 与对照组、PDAC-未治疗与对照组、PDAC-未治疗与 IPMN 组时,有 33、34 和 7 种差异表达蛋白,突出了补体系统和凝血系统的蛋白,如 C3、APOB 和 SERPINA。此外,与新辅助 Folfirinox 治疗或吉西他滨辅助治疗相比,未治疗的 PDAC 显示出 11 种差异表达蛋白。因此,在这里,我们在比较健康对照组时,在癌症患者(IPMN、PDAC)中发现了血浆外泌体衍生的差异表达蛋白,这可能代表了诊断和预后评估的替代生物标志物,支持对胰腺癌进行进一步的科学和临床研究。

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