Wang Q, Song B, Hao S, Xiao Z, Jin L, Zheng T, Chai F
Department of Thyroid Surgery, First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121001, China.
Department of Endocrinology and Metabolic Diseases, First Affiliated Hospital, Jinzhou Medical University, Jinzhou 121001, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2024 May 20;44(5):981-988. doi: 10.12122/j.issn.1673-4254.2024.05.21.
OBJECTIVE: To investigate cyclin D2 (CCND2) expression in papillary thyroid carcinoma (PTC) and its association with the clinicopathological features. METHODS: The public databases TCGA, TIMER 2.0 and UALCAN were used to explore CCND2 expression level in PTC and adjacent tissues, and its diagnostic value for PTC was analyzed using ROC curves. GO enrichment analysis of CCND2-related differentially expressed genes (DEGs) in PTC was performed, and tumor immune infiltration of CCND2 in thyroid cancer was analyzed using TIMER database and CIBERSORT data source. RT-qPCR and Western blot were used to detect CCND2 expression in normal human thyroid cell line Nthy-ori-3-1 and human PTC cell lines TPC-1 and BCPAP. CCND2 expression was also detected in clinical specimens of PTC and adjacent tissues by immunohistochemistry, and its correlation with clinicopathological features of the patients were analyzed. RESULTS: Informatic analysis revealed significantly higher CCND2 mRNA expression in thyroid cancer than in the adjacent tissues ( < 0.001) in close correlation with tumor stage, gender, age, pathological subtype, and lymph node involvement ( < 0.05). ROC curve analysis showed that at the cutoff value of 4.983, the diagnostic sensitivity, specificity, and accuracy of CCND2 expression for PTC was 83.6%, 94.9%, and 78.5%, respectively. CCND2 expression was positively correlated with B cells, CD4 T cells, and macrophages ( < 0.001) and negatively with CD8 T cells ( < 0.01), and also correlated with memory B-cell infiltration, CD4 T-cell memory activation, M2 macrophages, resting mast cells, and mast cell activation ( < 0.05). RT-qPCR, Western blot and immunohistochemistry showed significantly higher CCND2 expression in the PTC cells than in Nthy-ori-3-1 cells ( < 0.01) and also in clinical PTC tissues than in the adjacent tissues ( < 0.05) in correlation with tumor size, lymph node metastasis and TNM stage ( < 0.05). CONCLUSION: CCND2 overexpression is closely correlated with tumor progression and immune cell infiltration in PTC patients..
目的：探讨细胞周期蛋白D2（CCND2）在甲状腺乳头状癌（PTC）中的表达及其与临床病理特征的关系。 方法：利用公共数据库TCGA、TIMER 2.0和UALCAN探究PTC及癌旁组织中CCND2的表达水平，并使用ROC曲线分析其对PTC的诊断价值。对PTC中CCND2相关的差异表达基因（DEGs）进行基因本体（GO）富集分析，并利用TIMER数据库和CIBERSORT数据源分析甲状腺癌中CCND2的肿瘤免疫浸润情况。采用逆转录-定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法检测正常人甲状腺细胞系Nthy-ori-3-1及人PTC细胞系TPC-1和BCPAP中CCND2的表达。通过免疫组织化学检测PTC临床标本及癌旁组织中CCND2的表达，并分析其与患者临床病理特征的相关性。 结果：信息分析显示，甲状腺癌中CCND2 mRNA表达显著高于癌旁组织（<0.001），且与肿瘤分期、性别、年龄、病理亚型及淋巴结受累情况密切相关（<0.05）。ROC曲线分析表明，在截断值为4.983时，CCND2表达对PTC的诊断敏感性、特异性和准确性分别为83.6%、94.9%和78.5%。CCND2表达与B细胞、CD4 T细胞和巨噬细胞呈正相关（<0.001），与CD8 T细胞呈负相关（<0.01），还与记忆B细胞浸润、CD4 T细胞记忆激活、M2巨噬细胞、静息肥大细胞及肥大细胞激活相关（<0.05）。RT-qPCR、蛋白质免疫印迹法和免疫组织化学结果显示，PTC细胞中CCND2表达显著高于Nthy-ori-3-1细胞（<0.01），PTC临床组织中CCND2表达也高于癌旁组织（<0.05），且与肿瘤大小、淋巴结转移及TNM分期相关（<0.05）。 结论：CCND2过表达与PTC患者的肿瘤进展及免疫细胞浸润密切相关。
Nan Fang Yi Ke Da Xue Xue Bao. 2024-5-20
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