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.

中文翻译：

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基质辅助激光解吸/电离成像质谱方法研究甲状腺组织内与体重相关的变化

肥胖与许多合并症以及内分泌系统异常有关，更常见的是表现为甲状腺功能障碍，如甲状腺肿。体重的变化，尤其是体重的增加，可能会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询问瘦患者和肥胖患者甲状腺组织切片之间蛋白质分布和丰度的变化。从选定的病例和对照中鉴定出 FFPE 固定的甲状腺组织块，并将其作为基质辅助激光解吸/电离 (MALDI) 成像质谱 (IMS) 分析的目标。招募了 30 至 75 岁年龄组且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的患者被排除在研究之外。所选患者根据其 BMI 分为两组：瘦（BMI < 25）和肥胖（BMI > 35）。最初的试验集被用作优化 MALDI IMS 协议的试点研究，该协议接下来应用于选定的甲状腺组织。来自所有样本的 MALDI IMS 数据被对齐并进行了统计分析 最初的试验集被用作优化 MALDI IMS 协议的试点研究，该协议接下来应用于选定的甲状腺组织。来自所有样本的 MALDI IMS 数据被对齐并进行了统计分析 最初的试验集被用作优化 MALDI IMS 协议的试点研究，该协议接下来应用于选定的甲状腺组织。来自所有样本的 MALDI IMS 数据被对齐并进行了统计分析使用主成分分析 (PCA) 结果的k均值和线性判别分析 (LDA) 分类模型在两组之间进行评估：对照（瘦）和病例（肥胖）。接收者操作特征 (ROC) 曲线也可用于计算已鉴定肽的变异性。通过使用液相色谱和串联质谱 (LC-MS/MS) 分析，鉴别肽也被独立鉴定并与其相应的蛋白质相关。与肥胖组相比，发现主要来自甲状腺球蛋白的 8 种肽被上调，而在瘦肉组中发现另外 10 种肽被下调。通过这种技术，我们将能够更好地了解疾病实体与肥胖之间的关系。