血清TNF-α、IL-6、IL-4水平与三阴性乳腺癌病理特征的相关性及其对复发转移的预测价值

Serum Levels of TNF-α, IL-6, and IL-4 in Triple-Negative Breast Cancer: Correlation with Clinicopathological Features and Prediction Value of Recurrence and Metastasis

摘要: 目的：检测三阴性乳腺癌(Triple-negative breast cancer, TNBC)患者中血清TNF-α、IL-6、IL-4水平，分析其与临床病理特征的相关性，评估单项及联合检测对术后复发转移的预测效能。方法：回顾性纳入青岛大学附属医院诊断并进行治疗的57例TNBC患者，复发转移组13例，未复发转移组44例。所有患者均测定TNF-α、IL-6及IL-4水平，收集患者的临床病理资料。分析血清TNF-α、IL-6、IL-4水平与TNBC患者临床病理特征之间的相关性，不满足正态性或方差齐性的两组间比较采用非参数检验(Mann‑Whitney U检验)，多组间比较采用Kruskal‑Wallis H检验；分类变量行卡方检验或Fisher精确检验。通过ROC曲线评估血清TNF-α、IL-6及IL-4预测TNBC术后复发转移的价值。结果：不同临床分期、肿瘤大小、淋巴结转移、Ki-67表达与TNBC患者的血清TNF-α、IL-6、IL-4水平比较，差异有统计学意义(P < 0.05)，且血清TNF-α、IL-6及IL-4高水平与临床分期、肿瘤直径、淋巴结转移状态、Ki-67增殖指数及脉管癌栓状态均呈正相关(P < 0.05)。复发转移组患者血清TNF-α、IL-6、IL-4水平均高于未复发转移组(P < 0.05)。血清TNF-α、IL-6、IL-4预测TNBC复发转移的最佳截断值分别为2.215 pg/ml、2.930 pg/ml、1.325 pg/ml，对应的灵敏度与特异度分别为：TNF-α (0.538, 0.862)、IL-6 (0.615, 0.841)、IL-4 (0.769, 0.818)。三项联合预测TNBC复发转移的准确度高于单项检测(三项联合AUC = 0.850 vs. 单项AUC < 0.800)。结论：三阴性乳腺癌患者中，血清TNF-α、IL-6、IL-4水平与病理特征有相关性，血清TNF-α、IL-6、IL-4高水平与三阴性乳腺癌复发转移相关，是复发转移的危险因素，三项联合检测的预测效能优于单项检测，是潜在的无创预后评估组合标志物。

Abstract: Objective: To determine serum levels of TNF-α, IL-6, and IL-4 in triple-negative breast cancer (TNBC) patients, analyze their associations with clinicopathological features, and evaluate their predictive value for postoperative recurrence/metastasis. Methods: A retrospective cohort of 57 TNBC patients in the diagnosis and treatment by the Affiliated Hospital of Qingdao University (13 with recurrence/metastasis, 44 without) was enrolled. Serum TNF-α, IL-6, and IL-4 levels were measured, and clinicopathological data were collected. Correlations between serum cytokine levels and clinicopathological parameters were analyzed. For continuous variables with non-normal distribution or unequal variances, Mann-Whitney U test was used for two-group comparisons, and Kruskal-Wallis H test for multiple-group comparisons. Categorical variables were analyzed using chi-square test or Fisher’s exact test. The predictive performance of serum cytokines for TNBC recurrence and metastasis was evaluated by receiver operating characteristic (ROC) curve analysis. Results: Comparison of serum TNF-α, IL-6, and IL-4 levels among TNBC patients with different clinical stages, tumor sizes, lymph node metastasis statuses, and Ki-67 expression levels revealed statistically significant differences (all P < 0.05). Elevated serum levels of TNF-α, IL-6, and IL-4 were positively correlated with clinical stage, tumor diameter, lymph node metastasis, Ki-67 proliferation index, and tumor thrombus status (P < 0.05). Patients in the recurrence/metastasis group had significantly higher serum levels of TNF-α, IL-6, and IL-4 than those in the non-recurrence/metastasis group (P < 0.05). The optimal cutoff values for serum TNF-α, IL-6, and IL-4 in predicting TNBC recurrence/metastasis were 2.215 pg/mL, 2.930 pg/mL, and 1.325 pg/mL, respectively, yielding corresponding sensitivities and specificities as follows: TNF-α (0.538, 0.862), IL-6 (0.615, 0.841), and IL-4 (0.769, 0.818). The combined model of the three markers achieved higher predictive accuracy for TNBC recurrence/metastasis than any single marker (AUC for the combined model = 0.850 vs. AUC < 0.800 for each individual marker). Conclusion: In patients with triple-negative breast cancer, serum levels of TNF-α, IL-6, and IL-4 are correlated with pathological characteristics. High serum levels of these cytokines are associated with an increased risk of recurrence/metastasis and serve as risk factors. The combined detection of TNF-α, IL-6, and IL-4 offers superior predictive performance compared to single-marker detection, representing a potential non-invasive prognostic panel.