血清MMP-9、Foxp3水平与肺腺癌顺铂化疗敏感性及预后的关系-东南大学学报医学版

血清MMP-9、Foxp3水平与肺腺癌顺铂化疗敏感性及预后的关系

单位：郑州大学第一附属医院呼吸与危重症医学科, 河南郑州 450000

分类号：R734.2

出版年·卷·期（页码）：2025·44·第五期（773-780）

摘要：

目的:探讨血清基质金属蛋白酶-9(MMP-9)、叉状头/翅膀状螺旋转录因子(Foxp3)水平与肺腺癌顺铂化疗敏感性及预后的关系。方法:选取2021年1月至2024年1月我院接诊的肺腺癌患者153例,根据顺铂化疗敏感性将其分为不敏感组、敏感组。比较两组血清MMP-9、Foxp3水平及一般资料;采用多因素Logistic回归模型分析肺腺癌顺铂化疗敏感性的影响因素;绘制受试者工作特征(ROC)曲线,分析血清MMP-9、Foxp3单独及联合预测肺腺癌顺铂化疗敏感性的效能;绘制Kaplan-Meier曲线,分析血清MMP-9、Foxp3水平与肺腺癌预后的关系,并行Log-rank检验;采用Cox回归模型分析肺腺癌预后的影响因素。结果:153例患者中顺铂化疗敏感61例(敏感组),不敏感92例(不敏感组);不敏感组血清MMP-9、Foxp3水平均高于敏感组(P＜0.05);Logistic回归模型分析显示,美国东部肿瘤协作组(ECOG)体能状态评分、MMP-9、Foxp3是肺腺癌顺铂化疗敏感性的危险因素(P＜0.05);ROC曲线显示,血清MMP-9、Foxp3单独及联合预测肺腺癌顺铂化疗不敏感的AUC分别为0.708、0.717、0.816,Pairwise算法检验显示,与血清MMP-9、Foxp3单独预测比较,二者联合预测腺癌顺铂化疗不敏感的AUC均升高(Z=2.950,P=0.003 2;Z=3.130,P=0.001 7)。随访6~46个月,中位随访时间29个月,高、低MMP-9组中位生存时间分别为27个月(95% CI 22.842~31.158)、38个月(95% CI 27.099~48.901),低MMP-9组患者的生存时间长于高MMP-9组(χ²=6.977,P=0.008);高、低Foxp3组中位生存时间分别为30个月(95% CI 26.865~33.135)、38个月(95% CI 33.395~42.605),低Foxp3组的生存时间长于高Foxp3组(χ²=4.294,P=0.038)。Cox回归模型分析显示,年龄、Ki-67高阳性率、高MMP-9、高Foxp3是肺腺癌预后不良的危险因素(P＜0.05)。结论:血清MMP-9、Foxp3是肺腺癌顺铂化疗敏感性的危险因素,且与预后不良密切相关。

Objective: To investigate the association between serum matrix metalloproteinase-9(MMP-9) and forkhead/winged helix transcription factor(Foxp3) levels and the sensitivity to cisplatin chemotherapy, as well as their relationship with prognosis in patients with lung adenocarcinoma. Methods: A total of 153 patients diagnosed as lung adenocarcinoma treated at our hospital between January 2021 and January 2024 were enrolled in this retrospective study. Based on their response to cisplatin chemotherapy, the patients were divided into sensitive group and non-sensitive group. Serum levels of MMP-9 and Foxp3 and baseline clinical data were compared between the two groups. Multivariate Logistic regression model was employed to analyze the independent factors affecting cisplatin sensitivity. Receiver operating characteristic(ROC) curves were plotted to evaluate the predictive performance of MMP-9 and Foxp3 levels, both individually and in combination, for chemotherapy sensitivity. Kaplan-Meier survival curves were generated to assess the relationship between serum biomarker levels and patient prognosis, and Log-rank tests were performed for statistical comparison. Cox regression model was used to identify independent prognostic factors. Results: Among the 153 patients, 61 cases were sensitive to cisplatin chemotherapy(sensitive group) and 92 cases were insensitive to it(non-sensitive group). Serum levels of MMP-9 and Foxp3 were significantly higher in the non-sensitive group compared with the sensitive group(P<0.05). Logistic regression analysis indicated that eastern cooperative oncology group(ECOG) score and elevated levels of MMP-9 and Foxp3 were independent risk factors for reduced chemotherapy sensitivity(P<0.05). ROC curve analysis showed that the areas under the curve(AUCs) for MMP-9, Foxp3, and their combination in predicting chemotherapy non-sensitivity were 0.708, 0.717, and 0.816, respectively. Pairwise comparison revealed that the combined predictive value of MMP-9 and Foxp3 was significantly higher than either marker alone(Z=2.950, P=0.003 2; Z=3.130, P=0.001 7). During a follow-up period ranging from 6 to 46 months(median: 29 months), the median survival times for patients with high and low serum MMP-9 levels were 27 months(95% CI 22.842-31.158) and 38 months(95% CI 27.099-48.901), the survival time of patients in the low MMP-9 group was longer than that in the high MMP-9 group(χ²=6.977, P=0.008). Similarly, the median survival times for the high and low Foxp3 groups were 30 months(95% CI 26.865-33.135) and 38 months(95% CI 33.395-42.605), the survival time of the low Foxp3 group was longer than that of the high Foxp3 group(χ²=4.294, P=0.038). Cox regression analysis further identified age, high positive rate of ki-67, and elevated levels of MMP-9 and Foxp3 as independent prognostic factors associated with worse outcomes(P<0.05). Conclusion: Serum MMP-9 and Foxp3 levels are closely associated with cisplatin chemotherapy sensitivity and long-term prognosis in lung adenocarcinoma. Elevated levels of these biomarkers are independent risk factors for both reduced chemotherapy responsiveness and poor prognosis, suggesting their potential utility as predictive and prognostic indicators in clinical practice.

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