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通过生物信息学分析和机器学习鉴定和验证甲状腺乳头状癌和桥本甲状腺炎的潜在共同生物标志物。

Identification and validation of potential common biomarkers for papillary thyroid carcinoma and Hashimoto's thyroiditis through bioinformatics analysis and machine learning.

机构信息

Department of Ultrasound, The Second Affiliated Hospital of Anhui Medical Universty, Hefei, 230601, Anhui, China.

Dian Diagnostics Group Co., Ltd, Hangzhou, 310000, Zhejiang, China.

出版信息

Sci Rep. 2024 Jul 6;14(1):15578. doi: 10.1038/s41598-024-66162-2.

Abstract

There is a growing body of evidence suggesting that Hashimoto's thyroiditis (HT) may contribute to an increased risk of papillary thyroid carcinoma (PTC). However, the exact relationship between HT and PTC is still not fully understood. The objective of this study was to identify potential common biomarkers that may be associated with both PTC and HT. Three microarray datasets from the GEO database and RNA-seq dataset from TCGA database were collected to identify shared differentially expressed genes (DEGs) between HT and PTC. A total of 101 genes was identified as common DEGs, primarily enriched inflammation- and immune-related pathways through GO and KEGG analysis. We performed protein-protein interaction analysis and identified six significant modules comprising a total of 29 genes. Subsequently, tree hub genes (CD53, FCER1G, TYROBP) were selected using random forest (RF) algorithms for the development of three diagnostic models. The artificial neural network (ANN) model demonstrates superior performance. Notably, CD53 exerted the greatest influence on the ANN model output. We analyzed the protein expressions of the three genes using the Human Protein Atlas database. Moreover, we observed various dysregulated immune cells that were significantly associated with the hub genes through immune infiltration analysis. Immunofluorescence staining confirmed the differential expression of CD53, FCER1G, and TYROBP, as well as the results of immune infiltration analysis. Lastly, we hypothesise that benzylpenicilloyl polylysine and aspirinmay be effective in the treatment of HT and PTC and may prevent HT carcinogenesis. This study indicates that CD53, FCER1G, and TYROBP play a role in the development of HT and PTC, and may contribute to the progression of HT to PTC. These hub genes could potentially serve as diagnostic markers and therapeutic targets for PTC and HT.

摘要

越来越多的证据表明桥本甲状腺炎(HT)可能会增加甲状腺乳头状癌(PTC)的风险。然而,HT 和 PTC 之间的确切关系尚不完全清楚。本研究的目的是确定可能与 PTC 和 HT 都相关的潜在共同生物标志物。从 GEO 数据库中收集了三个微阵列数据集和 TCGA 数据库中的 RNA-seq 数据集,以确定 HT 和 PTC 之间共同的差异表达基因(DEG)。共鉴定出 101 个基因作为共同 DEG,通过 GO 和 KEGG 分析主要富集炎症和免疫相关途径。我们进行了蛋白质-蛋白质相互作用分析,并鉴定出包含总共 29 个基因的六个显著模块。随后,使用随机森林(RF)算法选择了三个树状枢纽基因(CD53、FCER1G、TYROBP),用于开发三个诊断模型。人工神经网络(ANN)模型表现出优异的性能。值得注意的是,CD53 对 ANN 模型输出的影响最大。我们使用人类蛋白质图谱数据库分析了这三个基因的蛋白质表达。此外,我们通过免疫浸润分析观察到与枢纽基因显著相关的各种失调免疫细胞。免疫荧光染色证实了 CD53、FCER1G 和 TYROBP 的差异表达,以及免疫浸润分析的结果。最后,我们假设苄青霉素多赖氨酸和阿司匹林可能对 HT 和 PTC 的治疗有效,并可能预防 HT 的癌变。本研究表明,CD53、FCER1G 和 TYROBP 在 HT 和 PTC 的发展中起作用,并可能有助于 HT 向 PTC 的进展。这些枢纽基因可能成为 PTC 和 HT 的诊断标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e8e/11227570/b23c018a8b4a/41598_2024_66162_Fig1_HTML.jpg

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