Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925 (98), Riyadh, 11461, Saudi Arabia.
Department of Medicine, College of Medicine, King Saud University, P.O. Box 2925 (38), Riyadh, 11461, Saudi Arabia.
J Mass Spectrom. 2021 Jan;56(1):e4671. doi: 10.1002/jms.4671. Epub 2020 Nov 10.
Obesity is associated with numerous comorbidities along with abnormalities of the endocrine system, more commonly manifesting as dysfunctions of the thyroid gland such as goiter. Changes in weight, especially an increase, could lead to an increase in the incidence of thyroid dysfunction; however, its pathophysiology remains to be elucidated. In the present study, we aimed to interrogate the changes in the protein distribution and abundance between the lean patients and patients with obesity thyroid tissue sections through utilizing this technique. The FFPE-fixed thyroid tissue blocks from the selected cases and controls were identified and targeted for matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) analysis. Patients in the 30 to 75 years age group and undergoing total thyroidectomy for benign thyroid disease were recruited. Patients with thyroid cancers, autoimmune disorders, and other inflammatory conditions were excluded from the study. The selected patients were divided into two groups according to their BMIs: lean (BMI < 25) and obese (BMI > 35). An initial trial set was used as a pilot study for the optimization of the MALDI IMS protocol that was next applied to the selected thyroid tissues. MALDI IMS data from all the samples were aligned and statistical analysis carried out by k-means and linear discriminant analysis (LDA) classification model using principle component analysis (PCA) results were evaluated between the two groups: controls (lean) and cases (obese). Receiver operator characteristic (ROC) curves were alternatively used to calculate the variability of the identified peptides. The discriminating peptides were also independently identified and related to their corresponding proteins by using liquid chromatography and tandem mass spectrometry (LC-MS/MS) analyses. Eight peptides mainly from thyroglobulin were found to be upregulated whereas 10 others were found to be downregulated in the lean compared to the obese group. Through this technique, we will be able to better understand the relationship between the disease entity and obesity.
肥胖与许多合并症相关，同时伴有内分泌系统异常，更常见的表现为甲状腺功能障碍，如甲状腺肿。体重变化，尤其是增加，可能导致甲状腺功能障碍的发生率增加；然而，其病理生理学仍有待阐明。在本研究中，我们旨在通过利用该技术研究瘦患者和肥胖患者甲状腺组织切片之间的蛋白质分布和丰度变化。从选定的病例和对照中识别并针对基质辅助激光解吸/电离（MALDI）成像质谱（IMS）分析选择 FFPE 固定的甲状腺组织块。招募了年龄在 30 至 75 岁之间并因良性甲状腺疾病接受全甲状腺切除术的患者。患有甲状腺癌、自身免疫性疾病和其他炎症性疾病的患者被排除在研究之外。根据 BMI 将选定的患者分为两组：瘦（BMI<25）和肥胖（BMI>35）。初始试验集用于优化 MALDI IMS 方案的初步研究，然后将其应用于选定的甲状腺组织。对所有样本的 MALDI IMS 数据进行对齐，并通过 k-均值和线性判别分析（LDA）分类模型进行统计分析，使用主成分分析（PCA）结果评估两组之间的差异：对照组（瘦）和病例组（肥胖）。还使用接收器操作特征（ROC）曲线计算鉴定肽的变异性。通过使用液相色谱和串联质谱（LC-MS/MS）分析，独立鉴定并将区分肽与相应的蛋白质相关联。与肥胖组相比，在瘦组中发现 8 种主要来自甲状腺球蛋白的肽上调，而其他 10 种肽下调。通过这项技术，我们将能够更好地理解疾病实体与肥胖之间的关系。
