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血小板衍生生长因子受体A(PDGFRA)在甲状腺乳头状癌中的临床及生物学作用:一项基于免疫组化和体外分析的研究

Clinical and biologic roles of PDGFRA in papillary thyroid cancer: a study based on immunohistochemical and in vitro analyses.

作者信息

Shi Lin, Chen Hao, Qin Yong-Ying, Gan Ting-Qing, Wei Kang-Lai

机构信息

Department of Pathology, The Second Affiliated Hospital of Guangxi Medical University Nanning, People's Republic of China.

Department of Medical Oncology, The Second Affiliated Hospital of Guangxi Medical University Nanning, People's Republic of China.

出版信息

Int J Clin Exp Pathol. 2020 May 1;13(5):1094-1107. eCollection 2020.

Abstract

BACKGROUND

Platelet-derived growth factor receptor alpha (PDGFRA) plays essential roles in several malignant tumors. Nevertheless, its clinical function in papillary thyroid cancer (PTC) is still unclear. This study aimed to examine the clinicopathologic implication and potential molecular underpinning of PDGFRA in PTC.

MATERIAL AND METHODS

Relative PDGFRA expression levels in eight cases of normal thyroid tissue, 15 cases of benign thyroid disease, and 90 cases of PTC were examined by immunohistochemistry (IHC). The prognostic value of PDGFRA was assessed by data mining of The Cancer Genome Atlas dataset. LV-PDGFRA overexpression and negative control CON220 lentivirus vectors were constructed and transfected into a PTC cell line. The capacity for cell proliferation, status of the cell cycle, efficiency of colony-forming, and migration ability of the PTC cells after PDGFRA were detected by multiple assays including methyl thiazolyl tetrazolium, flow cytometry, colony formation, transwell assay, and wound healing. Furthermore, bioinformatics analyses were conducted to determine the potential biologic mechanisms of PDGFRA.

RESULTS

Results of IHC showed that PDGFRA expression was significantly upregulated in PTC samples and was associated with an advanced pathologic stage. Furthermore, patients with PDGFRA overexpression showed poor survival. Ectopically overexpressed PDGFRA accelerated the migration and invasion of PTC cells. Results of the bioinformatics analyses suggested that PDGFRA was involved in several cell proliferation-related pathways.

CONCLUSION

Collectively, our results indicate that PDGFRA overexpression is associated with the poor survival of patients with PTC and that PDGFRA is a potent oncogene in PTC because it significantly increases PTC cell migration and invasion. Thus, PDGFRA may be a promising novel biomarker and therapeutic target for treating PTC.

摘要

背景

血小板衍生生长因子受体α(PDGFRA)在多种恶性肿瘤中发挥着重要作用。然而,其在甲状腺乳头状癌(PTC)中的临床功能仍不清楚。本研究旨在探讨PDGFRA在PTC中的临床病理意义及潜在的分子机制。

材料与方法

采用免疫组织化学(IHC)检测8例正常甲状腺组织、15例良性甲状腺疾病和90例PTC中PDGFRA的相对表达水平。通过挖掘癌症基因组图谱数据集评估PDGFRA的预后价值。构建LV-PDGFRA过表达和阴性对照CON220慢病毒载体,并将其转染到PTC细胞系中。通过甲基噻唑基四氮唑、流式细胞术、集落形成、Transwell实验和伤口愈合等多种实验检测PDGFRA过表达后PTC细胞的增殖能力、细胞周期状态、集落形成效率和迁移能力。此外,进行生物信息学分析以确定PDGFRA的潜在生物学机制。

结果

IHC结果显示,PTC样本中PDGFRA表达显著上调,且与病理分期进展相关。此外,PDGFRA过表达的患者生存率较差。异位过表达PDGFRA加速了PTC细胞的迁移和侵袭。生物信息学分析结果表明,PDGFRA参与了多个与细胞增殖相关的信号通路。

结论

总体而言,我们的结果表明,PDGFRA过表达与PTC患者的不良生存相关,并且PDGFRA是PTC中的一种强效癌基因,因为它显著增加了PTC细胞的迁移和侵袭。因此,PDGFRA可能是一种有前景的新型生物标志物和治疗PTC的靶点。

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