血清TLR4、TLR9作为化疗所致神经病理性疼痛生物学标记物的研究*

Serum TLR4 and TLR9 as biomarkers for chemotherapy-induced neuropathic pain

摘要:

目的 研究化疗患者血清中Toll样受体4(Toll-like receptor 4,TLR4)及Toll样受体9(Toll-like receptor 9,TLR9)的表达水平能否作为化疗所致神经病理性疼痛(Chemotherapy-induced neuropathic pain,CINP)的外周生物学标记物及二者对CINP患者疼痛程度的评估价值。方法：选取2021年11月至2022年1月本院收治的70例正在或既往接受化疗的肿瘤患者作为研究对象,根据患者是否存在化疗所致神经病理性疼痛分为CINP组(n=23)和无CINP组(n=47),比较两组一般资料并通过ELISA方法检测血清TLR4和TLR9浓度。结果：与无CINP组比较,CINP组血清TLR4和TLR9浓度较高。血清TLR4作为CINP标记物的诊断指标,ROC曲线下面积为0.723(P= 0.003),最佳临界值为20.99 ng/mL,敏感性为60.87%,特异性为72.34%。血清TLR9作为CINP诊断指标,ROC曲线下面积为0.776(P= 0.000),最佳临界值为22.54 ng/mL,敏感性为73.91%,特异性为78.72%。另外,CINP患者疼痛程度与血清TLR4和TLR9浓度均呈显著正相关(r= 0.637,P= 0.0011；r= 0.628,P= 0.0013)。Logistic回归分析显示,血清TLR4、TLR9是化疗患者发生CINP的影响因素。结论：化疗所致神经病理性疼痛患者血清TLR4、TLR9呈高水平表达状态,血清TLR4、TLR9有望成为诊断CINP的外周生物学指标。血清TLR4、TLR9表达水平与CINP患者疼痛程度有关,对临床镇痛药物的使用具有指导意义。

Abstract:

Objective To study whether the expression levels of Toll-like receptor 4 (TLR4) and Toll-like receptor 9 (TLR9) in sera of patients who received chemotherapy can be used as peripheral biological markers of chemotherapy-induced neuropathic pain (CINP) and their value in assessing the degree of pain in patients with CINP. Methods 70 tumor patients who were receiving or had received chemotherapy in our hospital from November 2021 to January 2022 were selected as the research object. According to the presence or absence of CINP, they were divided into CINP group (n = 23) and no CINP group (n = 47). The general data of the two groups were compared, and the concentrations of serum TLR4 and TLR9 were detected by ELISA. Results Serum TLR4 and TLR9 concentrations were higher in the CINP group compared to the no CINP group. The area under the ROC curve for serum TLR4 as a diagnostic indicator of CINP marker was 0.723 (P= 0.003), with a cut-off value 20.99 ng/mL, sensitivity of 60.87% and specificity of 72.34%. The area under the ROC curve for serum TLR9 as a diagnostic indicator of CINP was 0.776 (P= 0.000), with a cut-off value of 22.54 ng/mL, sensitivity of 73.91% and specificity of 78.72%. In addition, the degree of pain in CINP patients was significantly and positively correlated with both serum TLR4 and TLR9 concentrations (r= 0.637, P= 0.0011; r= 0.628, P= 0.0013). Logistic regression analysis showed that serum TLR4 and TLR9 were influential factors in the development of CINP in chemotherapy patients. Conclusions Patients with chemotherapy-induced neuropathic pain showed high levels of serum TLR4 and TLR9 expression, and serum TLR4 and TLR9 are expected to be peripheral biological indicators for the diagnosis of CINP. The expression levels of serum TLR4 and TLR9 are related to the degree of pain in patients with CINP and have implications for the use of clinical analgesic drugs.