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目的分析单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)及CC趋化因子受体2(CC chemokine receptor 2,CCR2)在人甲状腺乳头状癌(papillary thyroid carcinoma,PTC)合并桥本氏甲状腺炎(Hashimoto’s thyroiditis,HT)的表达,以探讨MCP-1/CCR2信号轴在HT-PTC发展过程中与PTC发生、发展相关的生物学作用。方法收集2013年6月至2014年6月在云南省第一人民医院乳腺及甲状腺肿瘤外科手术切除的人甲状腺新鲜组织(包括PTC组的癌组织、PTC-HT组的癌组织及病理证实的HT组的新鲜组织标本)及患者的外周血血清。运用实时荧光定量PCR、流式细胞微球芯片捕获技术(cytometric bead array,CBA)分析MCP-1/CCR2在人PTC、PTC-HT及HT组织和外周血血清的表达,表达谱基因芯片检测3组基因表达情况并进行多组差异基因筛选,构建共表达网络及显著性差异基因功能分析。结果①实时荧光定量PCR结果显示,CCR2 mRNA在HT甲状腺组织的表达水平(10.98±14.49)×10~(-3)明显高于PTC癌组织(2.63±4.97)×10~(-3)及PTC-HT癌组织[(3.77±4.65)×10~(-3),χ~2=3.78,P=0.03];PTC患者的CCR2 mRNA的表达水平与肿瘤直径呈负相关(P=0.01),与甲状腺球蛋白抗体(TGAb)及抗甲状腺过氧化物酶抗体(TPOAb)呈正相关(P=0.03,P=0.01);②CBA结果显示PTC-HT组患者外周血血清MCP-1的表达水平为(64.76±96.08)pg/m L,高于其他两组,但差异无统计学意义(F=1.04,P=0.36);③表达谱基因芯片结果显示,MCP-1 mRNA的表达水平在3组中差异无统计学意义(P>0.05),CCR2 mRNA的表达在HT组较其他两组明显升高(P=0.014,FDR=0.082),共表达网络分析表明与CCR2表达相关的差异基因共有8个,显著相关性功能主要集中在与免疫相关的19项功能通路中。结论 MCP-1/CCR2信号轴在HT-PTC发展过程中与PTC的发生无协同互作相关性,CCR2可能通过与TGAb和TPOAb的正相关关系发挥作用。
Objective To investigate the expression of monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor 2 (CC chemokine receptor 2) in human papillary thyroid carcinoma (PTC) To investigate the biological role of MCP-1 / CCR2 signaling axis in the development and progression of HT-PTC in combination with the expression of Hashimoto’s thyroiditis (HT). Methods The thyroid tissue freshly excised from June 2013 to June 2014 in the Department of Breast and Thyroid Surgery, Yunnan First People’s Hospital (including PTC tissues, PTC-HT tissues and pathologically confirmed HT Group of fresh tissue specimens) and the patient’s peripheral blood serum. The expression of MCP-1 / CCR2 in human PTC, PTC-HT and HT tissues and peripheral blood serum was analyzed by real-time fluorescence quantitative PCR and cytometric bead array (CBA) Group of gene expression and multi-group differential gene screening, construction of co-expression network and significant differences in gene function analysis. Results ① Real-time PCR showed that the expression of CCR2 mRNA in HT thyroid tissue was significantly higher than that in PTC tissue (2.63 ± 4.97) × 10 -3 and PTC (10.98 ± 14.49) × 10 -3 The expression of CCR2 mRNA in PTC patients was negatively correlated with tumor diameter (P = 0.01), but not with tumor size (3.77 ± 4.65 × 10 -3, χ 2 = 3.78, P = 0.03) The results of CBA showed that the expression of MCP-1 in peripheral blood of patients with PTC-HT was (64.76, P <0.01) ± 96.08) pg / m L, higher than the other two groups, but the difference was not statistically significant (F = 1.04, P = 0.36); ③Expression gene microarray results showed that the expression of MCP- The expression of CCR2 mRNA in HT group was significantly higher than that in other two groups (P = 0.014, FDR = 0.082). Co-expression network analysis showed that there were 8 different genes related to CCR2 expression, Significant correlations were found in 19 functional pathways related to immunity. Conclusion The signal axis of MCP-1 / CCR2 has no synergistic interaction with PTC in the development of HT-PTC, and CCR2 may play a role through the positive correlation with TGAb and TPOAb.