IGFBP3 as an indicator of lymph node metastasis and unfavorable prognosis for papillary thyroid carcinoma
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ORIGINAL ARTICLE
IGFBP3 as an indicator of lymph node metastasis and unfavorable prognosis for papillary thyroid carcinoma Yi Huang1 · Aoshuang Chang1 · Wei Zhou2 · Houyu Zhao1 · Xianlu Zhuo1 Received: 27 January 2020 / Accepted: 17 June 2020 © Springer Nature Switzerland AG 2020
Abstract Lymph node metastasis (LNM) is a usual event in papillary thyroid carcinoma (PTC) patients, which usually leads to poor prognosis. However, the molecular mechanisms of LNM remain unclear. Thus, we aimed to screen the possible key genes in the progression of LNM in PTC patients and further validate their roles. The study involved two phases: a discovery phase and a validation one. In the former phase, the candidate genes were screened by using bioinformatics methods. In the latter one, the genes were firstly assessed in a cohort from the cancer genome atlas (TCGA) to evaluate the associations of their expressions with clinical features and the prognostic values, and then, they were assessed at protein levels by using an immunohistochemical assay. Consequently, IGHBP3 was selected as the candidate gene, which might be enriched in several metabolism-related pathways and cancer progression-related pathways. High expressions of IGHBP3 have an association with gender, advanced clinical stages, high T stages, and the presence of LNM. Survival analysis indicated that IGHBP3 may affect the prognosis of PTC patients. The use of a tissue chip confirmed the view that IGHBP3 might play a crucial role in the LNM of PTC. In conclusion, IGHBP3 might be involved in the development of LNM in PTC patients. IGHBP3 over-expression might be a novel indicator and a potential target for PTC therapy. Keywords Papillary thyroid carcinoma · IGHBP3 · Tissue microarray · Immunohistochemistry · Bioinformatics method Abbreviations LNM Lymph node metastasis PTC Papillary thyroid carcinoma TCGA The cancer genome atlas IHC Immunohistochemical GEO Gene Expression Omnibus DEGs Differentially expressed genes GSEA Gene set enrichment analysis GO Gene ontology FDR False discovery rate PBS Phosphate buffer ANOVA Variance analysis IGFBP‐3 Insulin‐like growth factor binding protein‐3
* Xianlu Zhuo [email protected] 1
Affiliated Hospital of Guiyang Medical University, Guiyang, China
Chongqing Cancer Institute, Chongqing, China
2
Background Thyroid carcinoma is the most common endocrine malignant disorder in the world, and its incidence has increased in recent decades. Thyroid cancer can mainly be histologically classified into three types, namely, follicular thyroid cancer, papillary thyroid cancer (PTC), and anaplastic thyroid cancer [1]. The former two are well-differentiated, while the latter one is undifferentiated. Thus, the substantial characteristics of these pathological types are different. Of these types, PTC is the most common one, occupying about 80% of all thyroid cancers [2]. As a well-differentiated type of thyroid neoplasm, PTC often shows a favorable prognosis, especially in patients with young ages [3]. Nevertheless, a prop
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