Department of Otolaryngology Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
PLoS One. 2021 Jun 29;16(6):e0253943. doi: 10.1371/journal.pone.0253943. eCollection 2021.
To screen for obstructive sleep apnea (OSA) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-labeled quantitative proteomics assay was used to identify differentially expressed proteins (DEPs) during chronic intermittent hypoxia (CIH).
The iTRAQ technique was applied to compare DEPs in the serum of a CIH rat model and control group. Biological analysis of DEPs was performed using Gene Ontology and Kyoto Encyclopedia to explore related biological functions and signaling pathways. Enzyme-linked immunosorbent assay (ELISA) was performed to validate their expression in sera from patients with OSA and CIH rats.
Twenty-three DEPs (fold change ≥1.2 or ≤0.833, p<0.05) were identified, and two DEPs (unique peptides>3 and higher coverage) were further verified by ELISA in the CIH rat model and OSA subject: apolipoprotein A-IV (APOA4, p<0.05) and Tubulin alpha-1A chain (TUBA1A, p<0.05). Both groups showed significant differences in the expression levels of DEPs between the CIH and control groups and the severe OSA and non-OSA groups. APOA4 was found to be upregulated and TUBA1A downregulated in both the sera from OSA patients and CIH rats, on comparing proteomics results with clinical results. There were two pathways that involved three DEPs, the mitogen-activated protein kinase (MAPK) signaling pathway (p<0.05) and cytokine-cytokine receptor interaction (p<0.05).
APOA4 and TUBA1A may be potential novel biomarkers for CIH and OSA, and may play an important role in the development of OSA complications.
为了筛选阻塞性睡眠呼吸暂停（OSA）生物标志物，采用同位素相对和绝对定量（iTRAQ）标记定量蛋白质组学检测方法，鉴定慢性间歇性低氧（CIH）过程中的差异表达蛋白（DEPs）。
应用 iTRAQ 技术比较 CIH 大鼠模型和对照组血清中的 DEPs。采用基因本体论和京都基因与基因组百科全书对 DEPs 进行生物学分析，以探讨相关的生物功能和信号通路。采用酶联免疫吸附试验（ELISA）验证其在 OSA 患者和 CIH 大鼠血清中的表达。
在 CIH 大鼠模型中鉴定出 23 个 DEPs（倍数变化≥1.2 或≤0.833，p<0.05），其中两个 DEPs（独特肽>3 个且覆盖率较高）通过 ELISA 进一步验证：载脂蛋白 A-IV（APOA4，p<0.05）和微管蛋白 alpha-1A 链（TUBA1A，p<0.05）。CIH 组和对照组以及严重 OSA 和非 OSA 组之间，两组均显示 DEPs 的表达水平存在显著差异。在比较蛋白质组学结果与临床结果时，发现 OSA 患者和 CIH 大鼠血清中的 APOA4 上调，TUBA1A 下调。涉及三个 DEPs 的两条通路，有丝分裂原激活蛋白激酶（MAPK）信号通路（p<0.05）和细胞因子-细胞因子受体相互作用（p<0.05）。
APOA4 和 TUBA1A 可能是 CIH 和 OSA 的潜在新型生物标志物，可能在 OSA 并发症的发生发展中发挥重要作用。
