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通过蛋白质组学方法评估的胶质母细胞瘤诊断潜在血清生物标志物。

Potential serum biomarkers for glioblastoma diagnostic assessed by proteomic approaches.

作者信息

Popescu Ionela Daniela, Codrici Elena, Albulescu Lucian, Mihai Simona, Enciu Ana-Maria, Albulescu Radu, Tanase Cristiana Pistol

机构信息

Biochemistry-Proteomics Department, Victor Babes National Institute of Pathology, no 99-101 Splaiul Independentei, 050096 Sector 5, Bucharest, Romania ; Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, no. 91-95 Splaiul Independentei, 050095 Sector 5, Bucharest, Romania.

Biochemistry-Proteomics Department, Victor Babes National Institute of Pathology, no 99-101 Splaiul Independentei, 050096 Sector 5, Bucharest, Romania.

出版信息

Proteome Sci. 2014 Sep 24;12(1):47. doi: 10.1186/s12953-014-0047-0. eCollection 2014.

Abstract

BACKGROUND

The rapid progress of proteomics over the past years has allowed the discovery of a large number of potential biomarker candidates to improve early tumor diagnosis and therapeutic response, thus being further integrated into clinical environment. High grade gliomas represent one of the most aggressive and treatment-resistant types of human brain cancer, with approximately 9-12 months median survival rate for patients with grade IV glioma (glioblastoma). Using state-of-the-art proteomics technologies, we have investigated the proteome profile for glioblastoma patients in order to identify a novel protein biomarker panel that could discriminate glioblastoma patients from controls and increase diagnostic accuracy.

RESULTS

In this study, SELDI-ToF MS technology was used to screen potential protein patterns in glioblastoma patients serum; furthermore, LC-MS/MS technology was applied to identify the candidate biomarkers peaks. Through these proteomic approaches, three proteins S100A8, S100A9 and CXCL4 were selected as putative biomarkers and confirmed by ELISA. Next step was to validate the above mentioned molecules as biomarkers through identification of protein expression by Western blot in tumoral versus peritumoral tissue.

CONCLUSIONS

Proteomic technologies have been used to investigate the protein profile of glioblastoma patients and established several potential diagnostic biomarkers. While it is unlikely for a single biomarker to be highly effective for glioblastoma diagnostic, our data proposed an alternative and efficient approach by using a novel combination of multiple biomarkers.

摘要

背景

过去几年蛋白质组学的快速发展使得发现了大量潜在的生物标志物候选物,以改善肿瘤的早期诊断和治疗反应,从而进一步融入临床环境。高级别胶质瘤是人类脑癌中最具侵袭性和治疗抵抗性的类型之一,IV级胶质瘤(胶质母细胞瘤)患者的中位生存率约为9至12个月。我们使用最先进的蛋白质组学技术,研究了胶质母细胞瘤患者的蛋白质组图谱,以确定一种新型蛋白质生物标志物组合,该组合可以区分胶质母细胞瘤患者和对照组,并提高诊断准确性。

结果

在本研究中,表面增强激光解吸电离飞行时间质谱(SELDI-ToF MS)技术用于筛选胶质母细胞瘤患者血清中的潜在蛋白质模式;此外,液相色谱-串联质谱(LC-MS/MS)技术用于鉴定候选生物标志物峰。通过这些蛋白质组学方法,选择了三种蛋白质S100A8、S100A9和CXCL4作为假定的生物标志物,并通过酶联免疫吸附测定(ELISA)进行了确认。下一步是通过蛋白质印迹法鉴定肿瘤组织与瘤周组织中的蛋白质表达,以验证上述分子作为生物标志物。

结论

蛋白质组学技术已用于研究胶质母细胞瘤患者的蛋白质谱,并建立了几种潜在的诊断生物标志物。虽然单一生物标志物不太可能对胶质母细胞瘤诊断非常有效,但我们的数据提出了一种通过使用多种生物标志物的新型组合的替代且有效的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fc0/4189552/b498bc79e85d/12953_2014_47_Fig1_HTML.jpg

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