口腔鳞状细胞癌组织中miR-138、FOXD1表达与患者临床病理特征和预后的关系

Expression of miR-138 and FOXD1 in oral squamous cell carcinoma tissues and its relationship with pathological parameters and prognosis

目的探讨口腔鳞状细胞癌(OSCC)组织中微小核糖核酸-138(miR-138)、叉头框蛋白D1(FOXD1)的表达及与患者临床病理特征和预后的关系。方法收集行手术切除的80例OSCC患者癌组织和对应癌旁正常组织,采用实时荧光定量聚合酶链反应检测miR-138、FOXD1 mRNA表达。分析OSCC组织中miR-138、FOXD1 mRNA表达与患者临床病理特征的关系,根据OSCC组织中miR-138、FOXD1 mRNA表达均值分为高、低表达者。通过Tar-get Scan网站预测miR-138与FOXD1的结合位点。采用Pearson相关法分析OSCC组织中miR-138与FOXD1 mRNA表达的相关性,Kaplan-Meier法绘制不同miR-138、FOXD1 mRNA表达OSCC患者的生存曲线,多因素Cox回归分析OSCC患者预后的影响因素。结果与癌旁正常组织相比,OSCC组织中miR-138表达降低,FOXD1 mRNA表达升高(P均<0.05)。miR-138与FOXD1的3’非翻译端2942~2948处存在结合位点。Pearson相关性分析显示,OSCC组织中miR-138与FOXD1 mRNA表达呈负相关(r=-0.621,P<0.05)。不同分化程度、TNM分期、浸润深度、淋巴结转移OSCC组织中miR-138、FOXD1 mRNA表达比较差异有统计学意义(P均<0.05)。80例OSCC患者5年总生存率为55.00%(44/80)。Kaplan-Meier生存曲线分析显示,miR-138高表达者总生存率高于低表达者,FOXD1 mRNA高表达者总生存率低于低表达者(P均<0.05)。多因素Cox回归分析显示,低分化、TNM分期Ⅲ期、浸润深度≥5 cm、淋巴结转移、FOXD1 mRNA≥2.18为OSCC患者死亡的独立危险因素,miR-138≥0.78为独立保护因素(P均<0.05)。结论OSCC组织中miR-138低表达和FOXD1 mRNA高表达,二者表达与分化程度、TNM分期、浸润深度、淋巴结转移和预后有关,有望成为OSCC病情判断和预后评估的标志物。

Objective To investigate the expression of microRNA-138(miR-138)and forkhead box protein D1(FOXD1)in oral squamous cell carcinoma(OSCC)tissues and its relationship with pathological parameters and progno⁃sis.Methods Eighty cases of OSCC tissues and corresponding paracancerous tissues from OSCC patients that underwent surgical resection were collected as study subjects,and miR-138 and FOXD1 mRNA expression levels were detected by re⁃al-time fluorescence quantitative polymerase chain reaction.We analyzed the relationships between miR-138 and FOXD1 mRNA expression in OSCC tissues and clinicopathological features.OSCC tissues were divided into the high and low ex⁃pression groups according to the mean values of miR-138 and FOXD1 mRNA expression.The binding sites between miR-138 and FOXD1 were predicted by TargetScan.Pearson correlation was used to analyze the correlation between miR-138 and FOXD1 mRNA expression in OSCC tissues,Kaplan-Meier method was used to plot the survival curves of OSCC pa⁃tients with different miR-138 and FOXD1 mRNA expression,and multifactorial Cox regression was used to analyze the in⁃fluencing factors for the prognosis of OSCC patients.Results Compared with the paracancerous tissues,miR-138 expression decreased and FOXD1 mRNA expression increased in OSCC tissues(both P<0.05).MiR-138 had a binding site at the 3´untranslated end of FOXD1 at 2942-2948.Pearson correlation analysis showed that miR-138 was negatively corre⁃lated with FOXD1 mRNA expression in OSCC tissues(r=-0.621,P<0.001).Significant differences were found in the miR-138 and FOXD1 mRNA expression levels among OSCC tissues with different degrees of differentiation,TNM stage,depth of infiltration,and lymph node metastasis(all P<0.05).The 5-year overall survival rate of 80 patients with OSCC was 55.00%(44/80).Kaplan-Meier survival curve analysis showed that the overall survival rate was higher in the miR-138 high-expression group than in the low-expression group,and the overall survival rate was lower in the FOXD1 mRNA high-expression group than in the low-expression group(both P<0.05).Multifactorial Cox regression analysis showed that poor differentiation,TNM stage III,infiltration depth≥5 cm,lymph node metastasis,and FOXD1 mRNA≥2.18 were in⁃dependent risk factors for death in patients with OSCC,and miR-138≥0.78 was an independent protective factor(all P<0.05).Conclusion MiR-138 is low expressed and FOXD1 mRNA is highly expressed in OSCC tissues,which are asso⁃ciated with the degree of differentiation,TNM stage,depth of infiltration,lymph node metastasis,and prognosis,and may be markers for diagnosis and prognosis of OSCC patients.