术前血清MMP-9水平对HBV相关肝细胞癌患者肝切除术后生存的预测作用-东南大学学报医学版

术前血清MMP-9水平对HBV相关肝细胞癌患者肝切除术后生存的预测作用

单位：北京市房山区第一医院普外科, 北京 102400

分类号：R735.7;R512.62

出版年·卷·期（页码）：2022·41·第五期（652-659）

摘要：

目的：探讨术前基质金属蛋白酶-9（MMP-9）对乙型肝炎病毒相关肝细胞癌（HBV-HCC）患者肝切除术后生存的预测价值。方法：2012年1月至2016年11月，纳入868例HBV-HCC患者、250例慢性乙型肝炎（CHB）患者和277例健康志愿者分别作为HBV-HCC组、CHB组、健康对照组。所有HBV-HCC患者在我院普外科行根治性肝切除术。采用酶联免疫吸附试验检测术前血清MMP-9水平。分析MMP-9与HBV-HCC患者不同临床特征的关系，并收集至少5年的随访数据。结果：HBV-HCC组患者基线血清MMP-9水平显著高于CHB组和健康对照组（P<0.05）。经受试者工作特征（ROC）曲线分析，血清MMP-9水平用于区分CHB和HBV-HCC的曲线下面积（AUC）为0.726（95%CI：0.693~0.760），用于诊断HBV-HCC的AUC为0.773（95%CI：0.742~0.804）。术前血清MMP-9表达与患者肿瘤直径、病灶数量、BCLC分期、HBV-DNA载量、肝包膜浸润、分化程度、微血管浸润、微卫星不稳定有关（P<0.05）。高MMP-9组（≥74.60 ng·ml^-1）患者总生存期和无病生存期短于低MMP-9组（<74.60 ng·ml^-1）患者（P<0.001）。经Cox回归比例风险模型分析，术前血清MMP-9水平是HBV-HCC患者总生存和无病生存的独立影响因素（P<0.05）。结论：本研究结果支持MMP-9参与HBV-HCC的疾病进展，且血清MMP-9水平有可能成为预测HBV-HCC患者预后的生物标志物。

Objective: To investigate the predictive effect of preoperative matrix metalloproteinase-9 (MMP-9) on survival after hepatectomy in patients with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC). Methods: From January 2012 to November 2016, 868 patients with HBV-HCC, 250 patients with chronic hepatitis B(CHB) and 277 healthy volunteers were included as HBV-HCC group, CHB group and healthy control group respectively. All patients with HBV-HCC underwent radical hepatectomy in the general surgery department of our hospital. Serum MMP-9 level was detected by enzyme-linked immunosorbent assay. The relationship between MMP-9 and different clinical characteristics of HBV-HCC patients was analyzed and follow-up data were collected for at least 5 years. Results: The baseline serum MMP-9 level in HBV-HCC group was significantly higher than that in CHB group and healthy control group (P<0.05). According to the receiver operating characteristic (ROC) curve analysis, the area under the curve (AUC) of serum MMP-9 for distinguishing CHB and HBV-HCC was 0.726 (95%CI: 0.693-0.760), and the AUC for diagnosing HBV-HCC was 0.773 (95%CI: 0.742-0.804). The preoperative expression of serum MMP-9 was correlated with tumor diameter, number of lesions, BCLC stage, HBV-DNA load, hepatic capsule infiltration, degree of differentiation, microvascular infiltration and microsatellite instability (P<0.05). The total survival and disease-free survival of patients in the high MMP-9 group (≥ 74.60 ng·ml^-1) were shorter than those in the low MMP-9 group (<74.60 ng·ml^-1) (P<0.001). Cox regression proportional hazards model analysis showed that preoperative serum MMP-9 level was an independent influence factor for overall survival and disease-free survival in patients with HBV-HCC (P<0.05). Conclusion: These results support that MMP-9 would be involved in the disease progression of HBV-HCC, and the level of serum MMP-9 may be a biomarker to predict the prognosis of HBV-HCC patients.

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