基于中介效应分析预测术前血清IL-34、MMP-9水平对原发性肝癌临床分期及预后的影响

摘要/Abstract

摘要： 目的基于中介效应分析预测术前血清白细胞介素-34(IL-34)、基质金属蛋白酶-9(MMP-9)水平对原发性肝癌临床分期及预后的影响。方法以2017年6月至2021年6月在上海健康医学院附属崇明医院就诊的186例原发性肝癌患者为研究对象,根据临床分期将其分为I期组、Ⅱ期组、Ⅲ期组。在术后对研究对象进行随访,随访期间发生全因死亡者纳入预后不良组,反之纳入预后良好组。收集研究对象临床资料,检测术前血清IL-34、MMP-9水平。采用单因素和有序logistic回归分析探讨影响患者临床分期的独立影响因素。采用单因素和多因素Cox回归分析探讨影响患者预后不良的独立危险因素。将筛选出的同为影响患者临床分析及预后的变量作为协变量,分析中介效应。结果本研究纳入的186例患者中,12例患者失访,失访率为6.45%(12/186)。其余174例患者中,I期、Ⅱ期、Ⅲ期患者分别有45例、70例、59例,全因死亡52例,预后不良率为29.89(52/174)。单因素和多因素有序logistic回归分析结果显示,淋巴结转移、肿瘤大小(＞5 cm)、BCLC分期(C级)、低白蛋白、IL-34、MMP-9均是影响原发性肝癌患者临床分期进展的独立危险因素(P<0.05)。单因素和多因素Cox比例回归分析结果显示,淋巴结转移、肿瘤大小(＞5 cm)、BCLC分期(C级)、Child-Pugh分级(B级)、低白蛋白、IL-34、MMP-9均是影响原发性肝癌患者预后不良的独立危险因素(P<0.05)。将淋巴结转移、肿瘤大小、BCLC分期、低白蛋白作为协变量纳入中介效应模型,结果显示,术前血清IL-34、MMP-9对原发性肝癌患者的预后不良有正向预测作用(β=1.853、2.214,均P<0.001)。同时对患者临床分期具有正向预测作用(β=0.264、0.478,均P<0.001)。将临床分期代入模型后,术前血清IL-34、MMP-9水平对原发性肝癌患者预后不良有正向预测作用(β=2.436、3.108,均P<0.001)。直接效应分别占78.45%、82.36%,间接效应分别占21.55%、17.64%。结论术前血清IL-34、MMP-9水平越高,原发性肝癌患者预后不良风险越高。术前血清IL-34、MMP-9水平高可直接影响患者预后,也可通过影响临床分期间接影响患者预后。

关键词: 白细胞介素-34, 基质金属蛋白酶-9, 原发性肝癌, 临床分期, 预后, 中介分析

Abstract: Objective To predict the effects of preoperative serum interleukin-34 (IL-34) and matrix metalloproteinase-9 (MMP-9) levels on the clinical stage and prognosis of primary liver cancer (PLC) based on mediation effect analysis. Methods 186 patients with PLC were selected as subjects, all of whom were treated in Shanghai Health Medical College Affiliated Chongming Hospital from June 2017 to June 2021. The subjects were divided into stage I group, stage II group and stage III group according to clinical stage. The subjects were followed up after the operation. Those who died from all causes during the follow-up period were included in the poor prognosis group, and the remaining were assigned to the good prognosis group. The clinical data of the subjects were collected and the levels of serum IL-34 and MMP-9 were detected before operation. Univariate and ordered Logistic regression were used to analyze the independent factors affecting the clinical stage of patients. Univariate and multivariate Cox regression were used to analyze the independent risk factors for poor prognosis. The mediating effect was analyzed by screening out variables that affect both clinical analysis and prognosis of patients as covariables. Results Among the 186 patients included in this study, 12 patients were lost to follow up, with a loss rate of 6.45% (12/186). Among the other 174 patients, 45 patients were in stage I, 70 patients in stage II, 59 patients in stage III, and 52 patients died of all causes, with an adverse prognosis rate of 29.89% (52/174). Univariate and multivariate Logistic regression analysis showed that lymph node metastasis, tumor size (>5 cm), Barcelona Clinic Liver Cancer stage (BCLC stage C), low albumin, IL-34 and MMP-9 were all independent risk factors affecting the clinical stage progression of patients with PLC (P<0.05). Univariate and multivariate Cox regression analysis showed that lymph node metastasis, tumor size (>5 cm), BCLC stage (grade C), Child-Pugh grade (grade B), low albumin, IL-34 and MMP-9 were independent risk factors for poor prognosis in patients with PLC (P<0.05). Lymph node metastasis, tumor size, BCLC stage, and low albumin were included in the mediation effect model as covariables. The results showed that preoperative serum IL-34 and MMP-9 had a positive predictive effect on the poor prognosis of patients with primary liver cancer (β=1.853, 2.214, both P<0.001). They also had positive predictive effect on clinical stage (β=0.264, 0.478, P<0.001). After the clinical stage was included in the model, preoperative serum IL-34 and MMP-9 levels had a positive predictive effect on the poor prognosis of patients with primary liver cancer (β=2.436, 3.108, both P<0.001). Direct effect accounted for 78.45% and 82.36% respectively, indirect effect accounted for 21.55% and 17.64% respectively. Conclusion The higher the levels of serum IL-34 and MMP-9 before operation, the higher the risk of poor prognosis in patients with primary liver cancer. The higher the level of serum IL-34 and MMP-9 before operation can directly affect the prognosis of patients, and also indirectly affect the prognosis of patients through affecting the clinical stage.

Key words: Interleukin-34, Matrix metalloproteinase-9, Primary liver cancer, Clinical stage, Prognosis, Mediation analysis

胡刚峰, 王军, 章波, 王路兵, 黄磊. 基于中介效应分析预测术前血清IL-34、MMP-9水平对原发性肝癌临床分期及预后的影响[J]. 肝脏, 2026, 31(2): 234-241.

HU Gang-feng, WANG Jun, ZHANG Bo, WANG Lu-bing, HUANG Lei. Effects of preoperative serum IL-34 and MMP-9 levels on the clinical stage and prognosis of primary liver cancer based on mediation analysis[J]. Chinese Hepatolgy, 2026, 31(2): 234-241.

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