CXCR4 MFAP2 KLF4在分化型甲状腺癌中的表达及对预后的预测价值研究

doi:10.3969/j.issn.1006-6233.2024.03.013

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摘要 目的:研究趋化因子4受体(CXCR4)、微纤维相关蛋白2(MFAP2)、Krüppel样因子4(KLF4)在分化型甲状腺癌(DTC)中的表达及对预后的预测价值。方法:选择我院2019年7月至2020年7月收治的113例DTC患者,术中留取其肿瘤组织及癌旁正常组织。采用蛋白免疫印迹法检测DTC组织及癌旁正常组织中CXCR4、MFAP2、KLF4表达水平,分析CXCR4、MFAP2、KLF4表达水平与DTC临床病理特征的关系。对DTC患者进行3年随访,统计3年总生存情况,比较死亡组与存活组CXCR4、MFAP2、KLF4表达水平,采用ROC曲线分析CXCR4、MFAP2、KLF4对DTC预后的预测价值,采用Cox回归模型进行DTC预后单因素和多因素分析。结果:与癌旁正常组织比较,DTC组织CXCR4、MFAP2蛋白表达量显著升高(P<0.05),KLF4蛋白表达量显著降低(P<0.05)。TNM分期Ⅲ期、发生淋巴结转移、肿瘤低分化者CXCR4、MFAP2蛋白表达量显著高于TNM分期Ⅰ+Ⅱ期、未发生淋巴结转移、肿瘤中高分化者(P<0.05),TNM分期Ⅲ期、发生淋巴结转移、肿瘤低分化者KLF4蛋白表达量显著低于TNM分期Ⅰ+Ⅱ期、未发生淋巴结转移、肿瘤中高分化者(P<0.05)。113例DTC患者随访3年期间失访8例,最终获得随访者105例。死亡组患者CXCR4、MFAP2蛋白表达量显著高于存活组(P<0.05),KLF4蛋白表达量显著低于存活组(P<0.05)。绘制ROC曲线发现,CXCR4、MFAP2、KLF4单独或联合预测DTC预后的AUC(95%CI)分别为0.692(0.562~0.823)、0.729(0.590~0.869)、0.766(0.622~0.910)、0.832(0.690~0.975),联合预测的效能显著优于单项检测(P<0.05)。Cox回归分析显示,淋巴结转移、TNM分期Ⅲ期、肿瘤低分化、CXCR4表达升高、MFAP2表达升高、KLF4表达降低是DTC预后的危险因素(P<0.05)。结论:分化型甲状腺癌患者肿瘤组织中CXCR4、MFAP2呈高表达,KLF4呈低表达,其表达水平与淋巴结转移、肿瘤分化程度、TNM分期及3年总生存率相关,三者联合检测有助于预测分化型甲状腺癌预后。

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	顾占国
	李军
	梁金屏
	石福民

关键词 ：趋化因子4受体, 微纤维相关蛋白2, Krüppel样因子4, 分化型甲状腺癌, 表达水平, 预后, 预测价值

Abstract：Objective: To investigate the expression of chemokine 4 receptor (CXCR4), microfibril associated protein 2 (MFAP2), and Krüppel like factor 4 (KLF4) in differentiated thyroid cancer (DTC) and their predictive value for prognosis.Methods: A total of 113 patients with DTC admitted to our hospital from July 2019 to July 2020 were selected, and their tumor tissue and adjacent normal tissue were preserved during surgery. Protein immunoblotting was used to detect the expression levels of CXCR4, MFAP2, and KLF4 in DTC tissues and adjacent normal tissues. The relationship between the expression levels of CXCR4, MFAP2, and KLF4 and the clinical pathological characteristics of DTC was analyzed. The patients with DTC were followed up for 3 years, the overall survival was counted for 3 years, the expression levels of CXCR4, MFAP2, and KLF4 were compared between the death group and the survival group, and the predictive value of CXCR4, MFAP2, and KLF4 on the prognosis of DTC was analyzed by using the ROC curve, and the Cox regression model was used for the unifactorial and multifactorial analyses of the prognosis of DTC. Results: Compared with normal tissue adjacent to cancer, the expression of CXCR4 and MFAP2 proteins in DTC tissue was significantly increased ((P<0.05)), while the expression of KLF4 protein was significantly decreased((P<0.05)). The protein expression of CXCR4 and MFAP2 in TNM stage Ⅲ, lymph node metastasis, and poorly differentiated tumors was significantly higher than in TNM stage Ⅰ+Ⅱ, non-lymph node metastasis, and moderately well differentiated tumors ((P<0.05)). The protein expression of KLF4 in TNM stage Ⅲ, lymph node metastasis, and poorly differentiated tumors was significantly lower than in TNM stage Ⅰ+Ⅱ, non-lymph node metastasis, and moderately well differentiated tumors ((P<0.05)). During a 3-year follow-up period of 113 DTC patients, 8 cases were lost, and 105 cases were ultimately followed up. The expression of CXCR4 and MFAP2 proteins in the death group was significantly higher than those in the survival group (P<0.05), while the expression of KLF4 protein was significantly lower than in the survival group (P<0.05). Drawing the ROC curve, it was found that the AUC (95% CI) of CXCR4, MFAP2, and KLF4 alone or in combination to predict the prognosis of DTC were 0.692 (0.562~0.823), 0.729 (0.590~0.869), 0.766 (0.622~0.910), and 0.832 (0.690~0.975), respectively. The combined prediction performance was significantly better than the single detection (P<0.05). Cox regression analysis showed that lymph node metastasis, TNM stage Ⅲ, poor tumor differentiation, increased CXCR4 expression, increased MFAP2 expression, and decreased KLF4 expression were risk factors for the prognosis of DTC (P<0.05). Conclusion: CXCR4 and MFAP2 are highly expressed in tumor tissue of differentiated thyroid cancer patients, while KLF4 is low in expression. Their expression levels are related to lymph node metastasis, tumor differentiation, TNM staging, and 3-year overall survival rate. Combined detection of the three can help predict the prognosis of differentiated thyroid cancer.

Key words： Chemokine 4 receptor Microfiber associated protein 2 Krüppel like factor 4 Differentiated thyroid cancer Expression level Prognosis Predictive value

基金资助:河北省重点研发计划项目,(编号:22077710421D)

引用本文:

顾占国, 李军, 梁金屏, 石福民. CXCR4 MFAP2 KLF4在分化型甲状腺癌中的表达及对预后的预测价值研究[J]. 河北医学, 2024, 30(3): 423-428.
GU Zhanguo, LI Jun, LIANG jinping, et al. The Expression of CXCR4, MFAP2, and KLF4 in Differentiated Thyroid Cancer and Their Predictive Value for Prognosis. HeBei Med, 2024, 30(3): 423-428.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2024.03.013 或 http://www.hbyxzzs.cn/CN/Y2024/V30/I3/423

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