神经生长因子、酪氨酸激酶及B7-H4与宫颈癌病情进展、预后的关系研究

The relationship between the NGF,TrkA and B7-H4 and the progression and prognosis of cervical cancer

目的分析神经生长因子(NGF)、酪氨酸激酶(TrkA)及B7-H4与宫颈癌病情进展、预后的关系。方法纳入2016年6月至2018年6月我院收治的经术后病理确诊为宫颈癌的患者,收集肿瘤组织(癌组织组,n=109)及肿瘤旁的正常宫颈黏膜组织(癌旁正常组织组,n=109)。采用免疫组化法检测NGF、TrkA及B7-H4水平,比较NGF、TrkA及B7-H4在不同组织中的表达;分析NGF、TrkA及B7-H4与宫颈癌患者各病理参数的相关性,采用多元Logistic回归分析影响宫颈癌患者预后生存的危险因素;采用ROC分析NGF、TrkA及B7-H4对宫颈癌患者预后生存的预测价值。结果宫颈癌组织组NGF、TrkA及B7-H4阳性表达率显著高于癌旁正常组织组(P<0.05);有淋巴结转移、FIGO分期处于Ⅱa期、宫颈间质浸润深度>1/2 mm、组织分化为G2、G3的患者NGF、TrkA及B7-H4阳性表达率显著高于无淋巴结转移、FIGO分期处于Ⅰb期、宫颈间质浸润深度≤1/2 mm、组织分化为G1的患者,差异有统计学意义(P<0.05);109例患者经两年随访后显示,患者2年生存率为59.63%(65/109);经多元Logistic回归分析显示,FIGO分期、分化程度、淋巴转移、宫颈间质浸润深度、NGF、TrkA及B7-H4是影响患者预后的独立危险因素(P<0.05);ROC曲线显示NGF、TrkA及B7-H4三者联合曲线下面积分别为0.761、0.733、0738、0.853,各指标曲线下面积以联合检测最大。结论NGF、TrkA及B7-H4在宫颈癌组织中呈异常表达状态;其表达水平与患者的肿瘤临床病理特征及预后有关,可作为预测宫颈癌患者预后的分子标志物和潜在的治疗靶点。

Objective To analyze the relationship between the nerve growth factor(NGF),tyrosine kinase(TrkA)and B7-H4 and the progression and prognosis of cervical cancer.Methods Clinical data of 109 patients with cervical cancer diagnosed by postoperative pathology from June 2016 to June 2018 were collected.Tumor tissue(cancer tissue group,n=109)and normal cervical mucosa tissue adjacent to the tumor(normal tissue group adjacent to cancer,n=109)were collected.Immunohistochemical method was used to detect the levels of NGF,TrkA,and B7-H4.Theexpression of NGF,TrkA,and B7-H4 in different tissues was compared.Thecorrelation between the NGF,TrkA and B7-H4 and the pathological parameters of patients with cervical cancer was analyzed.Therisk factors affecting the prognostic survival of patients with cervical cancer were analyzed by using multivariate Logistic regression.ROC was used to analyze the predictive value of NGF,TrkA,and B7-H4 for the prognostic survival of patients with cervical cancer.Results The positive expression rates of NGF,TrkA and B7-H4 in the cervical cancer tissue group were significantly higher than those in the normal tissue group adjacent to cancer(P<0.05).The positive expression rates of NGF,TrkA and B7-H4 in patients with lymph node metastasis,FIGO staging in stage IIA,cervical stromal infiltration depth>1/2 mm,and tissue differentiation into G2 and G3 were significantly higher than those in patients without lymph node metastasis,FIGOstaging in stage IB,cervical stromal infiltration depth≤1/2 mm,and tissue differentiationinto G1(P<0.05).After 109 patients were followed up for two years,the results showed that the 2-year survival rate was 59.63%(65/109).Multivariate logistic regression analysis showed that FIGO stage,degree of differentiation,lymph node metastasis,depth of cervical stromal invasion,NGF,TrkA and B7-H4 were independent risk factors for prognosis(P<0.05).The ROC curve analysis showed that the area under the curve(AUC)of NGF,TrkA,B7-H4 and the three indexes combined were 0.761,0.733,0738 and 0.853,respectively,and the AUC of combined indexes was the largest.Conclusion NGF,TrkA,and B7-H4 are abnormally expressed in cervical cancer tissues.Their expression levelsare related to the clinicopathological characteristics and prognosis of the patients.They can be used as molecular markersfor predicting the prognosis of patients with cervical cancer and potential therapeutic targets.