Biomarker identification through spatial proteomics for the characterization of indeterminate thyroid nodules.

IF 2.9 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2025-08-11 DOI:10.1007/s12020-025-04383-9

Giulia Capitoli, Antonio Maria Alviano, Nicole Monza, Lisa Pagani, Isabella Piga, Davide Paolo Bernasconi, Angela Greco, Davide Leni, Alice Maggioni, Andrea-Valer Gatti, Fausto Maffini, Nicola Fusco, Mattia Garancini, Fulvio Magni, Stefania Galimberti, Fabio Pagni, Vincenzo L'Imperio, Vanna Denti

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引用次数: 0

Abstract

Purpose: The identification of novel molecular biomarkers may assist in the characterization of indeterminate thyroid nodules, which pose significant diagnostic challenges. Here, we aimed to explore the potential of proteomic analyses to support biomarker discovery in challenging thyroid lesions.

Methods: Linear Discriminant Analysis (LDA) was applied to Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) data from 44 thyroid neoplasms to select the most impactful molecular features for the classification of different tumor histologies, as well as for the distinction between NRAS-mutant (mNRAS) and NRAS-wild-type (wtNRAS) tumors. Relevant peaks were subsequently identified through nanoscale liquid chromatography electrospray ionization tandem mass spectrometry (nLC-ESI-MS/MS).

Results: The LDA selected nine relevant molecular markers distinguishing noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) from other tumor histologies (balanced accuracy = 73%), as well as 19 relevant markers able to identify mNRAS cases (balanced accuracy = 84%). Nine differentially expressed proteins were putatively identified: among them, ATP-dependent RNA helicase DDX42 showed a similar distribution between NIFTPs and papillary thyroid carcinomas (PTCs) / follicular variant PTCs (FVPTCs), while the distribution of the Histone H4 signal was similar between NIFTPs and follicular adenomas (FAs). In addition, Protein disulfide-isomerase A1 and Complement C4-B were overexpressed in wtNRAS compared to mNRAS cases, regardless of histology.

Conclusion: The LDA-selected features enable to distinguish NIFTPs from morphologically similar lesions and to discriminate between mNRAS and wtNRAS cases. The identified markers might complement genetic analyses and provide insights into the distinct pathogenic drivers behind the development of mNRAS compared to wtNRAS lesions.

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通过空间蛋白质组学鉴定不确定甲状腺结节的生物标志物。

目的：鉴定新的分子生物标志物可能有助于不确定甲状腺结节的特征，这对诊断提出了重大挑战。在这里，我们旨在探索蛋白质组学分析的潜力，以支持在挑战性甲状腺病变中发现生物标志物。方法：对44例甲状腺肿瘤的基质辅助激光解吸电离质谱成像（MALDI-MSI）数据进行线性判别分析（LDA），选择最具影响的分子特征用于不同肿瘤组织学的分类，以及nras -突变型（mNRAS）和nras -野生型（wtNRAS）肿瘤的区分。随后通过纳米级液相色谱-电喷雾电离串联质谱（nLC-ESI-MS/MS）鉴定了相关峰。结果：LDA选择了9个区分具有乳头状样核特征的非侵袭性滤泡性甲状腺肿瘤（NIFTPs）与其他肿瘤组织学的相关分子标记（平衡准确率为73%），以及19个能够识别mNRAS病例的相关标记（平衡准确率为84%）。推测鉴定出9种差异表达蛋白，其中atp依赖性RNA解旋酶DDX42在NIFTPs和甲状腺乳头状癌(ptc) /滤泡变异型ptc （fvptc）之间分布相似，Histone H4信号在NIFTPs和滤泡腺瘤（FAs）之间分布相似。此外，与mNRAS病例相比，无论组织学如何，wtNRAS中蛋白二硫异构酶A1和补体C4-B均过表达。结论：lda选择的特征能够区分NIFTPs与形态相似的病变，并区分mNRAS和wtNRAS病例。鉴定的标记物可能补充遗传分析，并提供与wtNRAS病变相比，mNRAS病变发展背后的独特致病驱动因素的见解。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.