SPON2在甲状腺乳头状癌中的表达及其临床意义

doi:10.3969/j.issn.1004-616x.2023.01.002

摘要/Abstract

摘要： 目的: 探讨脊椎蛋白2(SPON2)在甲状腺乳头状癌(PTC)中的表达及其临床意义。方法: 收集PTC及其癌旁组织新鲜手术标本7例，用实时荧光定量PCR(qPCR)检测PTC及其癌旁组织中SPON2 mRNA的表达情况。并选取2019—2020年间病理科存档PTC石蜡标本68例，采用免疫组织化学SP 法检测SPON2蛋白在PTC 中的表达情况；并使用Kaplan Meier-Plotter 数据库分析SPON2mRNA表达水平与甲状腺癌患者的预后关系。使用GEPIA数据库分析SPON2 mRNA表达水平与甲状腺癌临床分期之间的关系。使用TIMER数据库分析SPON2 mRNA表达水平与甲状腺癌免疫细胞之间的关系。结果: qPCR结果显示，PTC组织SPON2 mRNA相对表达水平为1.705±0.724，明显高于癌旁组织的0.929±0.278，差异具有统计学意义(P=0.036)。免疫组化结果显示，SPON2蛋白表达于细胞质及细胞外基质中，在PTC中的表达显著高于癌旁组织，差异具有统计学意义(P<0.01)。通过GEPIA数据库分析发现，SPON2 mRNA表达差异与甲状腺癌临床分期相关(P=0.002)。Kaplan Meier-Plotter数据库显示，在502例甲状腺癌病例中，SPON2mRNA高表达较低表达患者的生存预后更差(P=0.026)。TIMER数据库分析显示，SPON2 mRNA表达与甲状腺癌肿瘤纯度无明显相关(P=0.135)，而与B细胞、CD8⁺ T细胞、CD4⁺ T细胞、巨噬细胞、中性粒细胞、树突状细胞浸润以及M2巨噬细胞标志物CD68、CD163、CD206呈正相关(均为P<0.01)。结论: SPON2在PTC组织中高表达，SPON2高表达甲状腺癌患者预后不良，SPON2可能通过M2巨噬细胞及其他免疫细胞促进甲状腺癌进展。SPON2可能成为临床上新的甲状腺癌诊断标志物。

关键词: 脊椎蛋白2, 甲状腺癌, 甲状腺乳头状癌, 免疫细胞, 预后, 免疫组化

Abstract: OBJECTIVE: To investigate expression of spondin 2 (SPON2) in papillary thyroid carcinomas (PTC) and its clinical significance. METHODS: Seven fresh surgical specimens of PTC and adjacent tissues were collected. real-time quantitative PCR (qPCR) was used to detect mRNA expression of SPON2 in the tissues. From 2019-2020，68 cases of PTC paraffin specimens were collected from the Department of Pathology and expression of SPON2 protein in the specimens were detected using the immunohistochemical SP method. Prognostic relationships between SPON2 mRNA expression levels and thyroid cancers were evaluated using the Kaplan Meier-Plotter database. Relationships between SPON2 mRNA expression levels and clinical stages were analyzed using the GEPIA database. Relationships between SPON2 mRNA expression levels and thyroid cancer immune cells were analyzed using the TIMER database. RESULTS: The qPCR results showed that the mRNA expression levels of SPON2 were significantly higher in PTC tissues (1.705 ± 0.724) than in paraneoplastic tissues (0.929±0.278) (P=0.036). Immunohistochemical results showed that SPON2 protein was expressed in the cytoplasm and the extracellular matrix， and their expressions were significantly higher in PTC than in its paracancerous tissues (P<0.001). Analysis of the GEPIA database revealed that differences in SPON2 mRNA expression correlated with clinical stages of the cancers (P=0.002). The Kaplan Meier-Plotter database showed that， in 502 thyroid cancer cases， prognostic survival was worse in patients with high SPON2 mRNA expressions than with low expressions (P=0.026). TIMER database analysis showed that SPON2 mRNA expressions did not correlate significantly with thyroid cancer tumor purity (P=0.135)， but positively and significantly correlated with B cells， CD8⁺ T cells， CD4⁺ T cells， macrophages， neutrophils， dendritic cell infiltration，and the M2 macrophage markers CD68，CD163，and CD206 (P<0.001). CONCLUSION: SPON2 was highly expressed in PTC cancer tissues. Thyroid cancer patients with high SPON2 expressions had poor prognosis. SPON2 might have promoted progression of thyroid cancers through M2 macrophages and other immune cells. SPON2 may be a new marker for diagnosis of thyroid cancers， for evaluating clinical stages and prognosis of the cancers and for therapeutic target.

Key words: SPON2, thyroid cancer, papillary thyroid carcinoma, immune cells, prognosis, immunohistochemical

中图分类号:

R736.1

胡学义, 沈丰, 武伦, 苏才武, 魏涧. SPON2在甲状腺乳头状癌中的表达及其临床意义[J]. 癌变·畸变·突变, 2023, 35(1): 9-14.

HU Xueyi, SHEN Feng, WU Lun, SU Caiwu, WEI Jian. SPON2 expression in papillary thyroid carcinomas and its clinical significance[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(1): 9-14.

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