目的 探讨共刺激分子B7同源体4（B7-H4）、神经生长因子（NGF）、人附睾蛋白4（HE4）、酪氨酸激酶（TrkA）表达水平与宫颈癌病情进展、预后的关系。方法 选取2019-01至2022-12在北部战区总医院行宫颈癌根治术患者102例为研究对象,取术中切除的肿瘤组织作为标本,采用免疫组化法检测B7-H4、NGF、HE4、TrkA表达水平,比较不同FIGO分期、肿瘤分级、是否伴淋巴结转移患者宫颈组织B7-H4、NGF、HE4、TrkA表达。所有患者均随访至2024-06,比较死亡与存活患者宫颈组织B7-H4、NGF、HE4、TrkA表达差异。结果 Ⅱb期19例,IⅡa期29例,Ib期31例,Ia期23例,不同FIGO分期患者B7-H4、NGF、TrkA 、HE4表达水平比较,差异有统计学意义。肿瘤分级G1级27例,G2级50例,G3级25例,不同肿瘤分级患者B7-H4、NGF、TrkA、HE4表达水平比较,差异有统计学意义。浸润深度59例≤1/2,43例>1/2,浸润深度>1/2患者与浸润深度≤1/2患者中B7-H4、NGF、TrkA、HE4表达水平比较,差异有统计学意义（P<0.05）。无淋巴结转移61例,有淋巴结转移41例,有淋巴结转移患者与无淋巴结转移患者中B7-H4、NGF、TrkA、HE4表达水平比较,差异有统计学意义（P<0.05）。所有患者均随访至2023-12,平均随访62.4个月,存活58例（56.86%）,死亡44例（43.14%）。存活组与死亡组B7-H4、NGF、TrkA、HE4阳性表达水平比较,差异有统计学意义（P<0.05）。建立 R0C 曲线,B7-H4、NGF、HE4、TrkA单独预测宫颈癌患者预后的AUC（95%CI）分别为0.782（0.696~0.889）、0.741（0.637~0.846）、0.625（0.506~0.744）、0.797（0.696~0.898）,均有预测价值。联合预测的 AUC（95%CI）为0.919（0.856~0.982）,高于单独预测。结论 B7-H4、NGF、HE4、TrkA预测宫颈癌患者预后有一定价值,联合预测可提高预测的敏感度和特异度,可作为预测病情进展和预后的分子标志物的潜在靶点。

Objective To study the relationship between the expression levels of costimulatory molecule B7 homolog 4 （B7-H4）, nerve growth factor （NGF）, human epididymis protein 4 （HE4）, and tyrosine kinase （TrkA） and the progression and prognosis of cervical cancer. Methods A total of 102 patients who underwent radical hysterectomy for cervical cancer at General Hospital of PLA Northern Theater Command from January 2019 to December 2022 were selected, and their tumor tissues removed during the operation were used as samples. The expression of B7-H4, NGF, HE4 and TrkA was detected by immunohistochemistry. The expression levels of B7-H4, NGF, HE4 and TrkA in cervical tissues of patients with different FIGO stages, tumor grades, and whether accompanied by lymph node metastasis was compared. All the patients were followed up until June 2024, and the differences in the expression of B7-H4, NGF, HE4 and TrkA in cervical tissues between the dead and surviving patients were compared. Results Among the 102 patients, 19 were stage IIb, 29 were stage IIa, 31 were stage Ib, and 23 were stage Ia. Expression levels of B7-H4, NGF, TrkA and HE4 differed significantly across the different FIGO stages （P< 0.05）.Histologic grading was G1 in 27 cases, G2 in 50 cases and G3 in 25 cases. Expression levels of B7-H4, NGF, TrkA and HE4 varied significantly among the different tumour grades （P < 0.05）.Depth of cervical stromal invasion was ≤ 1/2 in 59 patients and > 1/2 in 43 patients. Expression levels of B7-H4, NGF, TrkA and HE4 were significantly higher in patients with invasion > 1/2 than in those with invasion ≤ 1/2 （P < 0.05）.Lymph-node metastasis was absent in 61 patients and present in 41 patients. Expression levels of B7-H4, NGF, TrkA and HE4 were significantly higher in patients with lymph-node metastasis than in those without （P < 0.05）.All patients were followed up until December 2023 （mean follow-up, 62.4 months）. At the last follow-up, 58 patients （56.86 %） were alive and 44 （43.14 %） had died. Expression levels of B7-H4, NGF, TrkA and HE4 were significantly different between the survival and death groups （P < 0.05）.ROC curves were constructed to evaluate the prognostic performance of each biomarker. The area under the curve （AUC） with 95 % confidence interval （CI） was 0.782 （0.696-0.889） for B7-H4, 0.741 （0.637-0.846） for NGF, 0.625 （0.506-0.744） for HE4 and 0.797 （0.696-0.898） for TrkA, indicating that each marker independently predicted prognosis. The combined model yielded an AUC （95 % CI） of 0.919 （0.856-0.982）, superior to that of any single marker alone. Conclusion B7-H4, NGF, HE4, and TrkA have certain value in predicting the prognosis of cervical cancer patients. Combined prediction can improve the sensitivity and specificity of prediction and can be used as molecular markers for predicting disease progression and prognosis and potential therapeutic targets.