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胶质纤维酸性蛋白、神经丝轻链、基质金属蛋白酶3和脂肪酸结合蛋白4作为无创性脑肿瘤生物标志物。

Glial fibrillary acidic protein, neurofilament light, matrix metalloprotease 3 and fatty acid binding protein 4 as non-invasive brain tumor biomarkers.

作者信息

Ghorbani Atefeh, Chatanaka Miyo K, Avery Lisa M, Wang Mingyue, Brown Jermaine, Cohen Rachel, Gorham Taron, Misaghian Salvia, Padmanabhan Nikhil, Romero Daniel, Stengelin Martin, Mathew Anu, Sigal George, Wohlstadter Jacob, Horbinski Craig, McCortney Katy, Xu Wei, Zadeh Gelareh, Mansouri Alireza, Yousef George M, Diamandis Eleftherios P, Prassas Ioannis

机构信息

Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.

Biostatistics Division, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.

出版信息

Clin Proteomics. 2024 Jun 15;21(1):41. doi: 10.1186/s12014-024-09492-7.

Abstract

BACKGROUND

Gliomas are aggressive malignant tumors, with poor prognosis. There is an unmet need for the discovery of new, non-invasive biomarkers for differential diagnosis, prognosis, and management of brain tumors. Our objective is to validate four plasma biomarkers - glial fibrillary acidic protein (GFAP), neurofilament light (NEFL), matrix metalloprotease 3 (MMP3) and fatty acid binding protein 4 (FABP4) - and compare them with established brain tumor molecular markers and survival.

METHODS

Our cohort consisted of patients with benign and malignant brain tumors (GBM = 77, Astrocytomas = 26, Oligodendrogliomas = 23, Secondary tumors = 35, Meningiomas = 70, Schwannomas = 15, Pituitary adenomas = 15, Normal individuals = 30). For measurements, we used ultrasensitive electrochemiluminescence multiplexed immunoassays.

RESULTS

High plasma GFAP concentration was associated with GBM, low GFAP and high FABP4 were associated with meningiomas, and low GFAP and low FABP4 were associated with astrocytomas and oligodendrogliomas. NEFL was associated with progression of disease. Several prognostic genetic alterations were significantly associated with all plasma biomarker levels. We found no independent associations between plasma GFAP, NEFL, FABP4 and MMP3, and overall survival. The candidate biomarkers could not reliably discriminate GBM from primary or secondary CNS lymphomas.

CONCLUSIONS

GFAP, NEFL, FABP4 and MMP3 are useful for differential diagnosis and prognosis, and are associated with molecular changes in gliomas.

摘要

背景

胶质瘤是侵袭性恶性肿瘤,预后较差。对于发现用于脑肿瘤鉴别诊断、预后评估和治疗管理的新型非侵入性生物标志物仍存在未满足的需求。我们的目标是验证四种血浆生物标志物——胶质纤维酸性蛋白(GFAP)、神经丝轻链(NEFL)、基质金属蛋白酶3(MMP3)和脂肪酸结合蛋白4(FABP4)——并将它们与已确立的脑肿瘤分子标志物及生存率进行比较。

方法

我们的队列包括患有良性和恶性脑肿瘤的患者(胶质母细胞瘤=77例,星形细胞瘤=26例,少突胶质细胞瘤=23例,继发性肿瘤=35例,脑膜瘤=70例,神经鞘瘤=15例,垂体腺瘤=15例,正常个体=30例)。为进行测量,我们使用了超灵敏电化学发光多重免疫测定法。

结果

血浆GFAP浓度高与胶质母细胞瘤相关,GFAP浓度低和FABP4浓度高与脑膜瘤相关,GFAP浓度低和FABP4浓度低与星形细胞瘤和少突胶质细胞瘤相关。NEFL与疾病进展相关。几种预后相关的基因改变与所有血浆生物标志物水平均显著相关。我们发现血浆GFAP、NEFL、FABP4和MMP3与总生存率之间无独立关联。候选生物标志物无法可靠地区分胶质母细胞瘤与原发性或继发性中枢神经系统淋巴瘤。

结论

GFAP、NEFL、FABP4和MMP3对鉴别诊断和预后评估有用,且与胶质瘤的分子变化相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1105/11179213/26895e278390/12014_2024_9492_Fig1_HTML.jpg

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