Thumbigere-Math V, Michalowicz B S, de Jong E P, Griffin T J, Basi D L, Hughes P J, Tsai M L, Swenson K K, Rockwell L, Gopalakrishnan R
Division of Periodontology, University of Minnesota School of Dentistry, Minneapolis, MN, USA.
Oral Dis. 2015 Jan;21(1):46-56. doi: 10.1111/odi.12204. Epub 2013 Nov 29.
The objective of this study was to identify differentially expressed salivary proteins in bisphosphonate-related osteonecrosis of the jaw (BRONJ) patients that could serve as biomarkers for BRONJ diagnosis.
Whole saliva obtained from 20 BRONJ patients and 20 controls were pooled within groups. The samples were analyzed using iTRAQ-labeled two-dimensional liquid chromatography-tandem mass spectrometry.
Overall, 1340 proteins were identified. Of these, biomarker candidates were selected based on P-value (<0.001), changes in protein expression (≥1.5-fold increase or decrease), and unique peptides identified (≥2). Three comparisons made between BRONJ and control patients identified 200 proteins to be differentially expressed in BRONJ patients. A majority of these proteins were predicted to have a role in drug metabolism and immunological and dermatological diseases. Of all the differentially expressed proteins, we selected metalloproteinase-9 and desmoplakin for further validation. Immunoassays confirmed increased expression of metalloproteinase-9 in individual saliva (P = 0.048) and serum samples (P = 0.05) of BRONJ patients. Desmoplakin was undetectable in saliva. However, desmoplakin levels tended to be lower in BRONJ serum than controls (P = 0.157).
Multiple pathological reactions are involved in BRONJ development. One or more proteins identified by this study may prove to be useful biomarkers for BRONJ diagnosis. The role of metalloproteinase-9 and desmoplakin in BRONJ requires further investigation.
本研究的目的是鉴定双膦酸盐相关颌骨坏死（BRONJ）患者中差异表达的唾液蛋白，这些蛋白可作为BRONJ诊断的生物标志物。
将20例BRONJ患者和20例对照者的全唾液按组进行混合。使用iTRAQ标记的二维液相色谱 - 串联质谱对样本进行分析。
总体而言，共鉴定出1340种蛋白质。其中，基于P值（<0.001）、蛋白质表达变化（≥1.5倍增加或减少）和鉴定出的独特肽段（≥2）选择生物标志物候选物。BRONJ患者与对照患者之间进行的三项比较确定了200种在BRONJ患者中差异表达的蛋白质。这些蛋白质中的大多数预计在药物代谢以及免疫和皮肤病中起作用。在所有差异表达的蛋白质中，我们选择基质金属蛋白酶 - 9和桥粒斑蛋白进行进一步验证。免疫测定证实BRONJ患者个体唾液（P = 0.048）和血清样本（P = 0.05）中基质金属蛋白酶 - 9的表达增加。在唾液中未检测到桥粒斑蛋白。然而，BRONJ患者血清中桥粒斑蛋白水平往往低于对照组（P = 0.157）。
BRONJ的发生涉及多种病理反应。本研究鉴定出的一种或多种蛋白质可能被证明是BRONJ诊断的有用生物标志物。基质金属蛋白酶 - 9和桥粒斑蛋白在BRONJ中的作用需要进一步研究。
