原发性肝癌患者血清DNMT1、M2BPGi的表达及其与预后的关系

摘要/Abstract

摘要： 目的探讨原发性肝癌(PLC)患者血清中DNA甲基转移酶1(DNMT1)、Mac-2结合蛋白糖基化异构体(M2BPGi)的表达水平及其与预后的关系。方法选取2020年5月至2021年5月唐山市人民医院收治的PLC患者79例。另选择同期37名健康体检者作为对照。比较两组研究对象血清中DNMT1、M2BPGi的表达水平,并分析其与PLC患者的临床病理特征关系;采用受试者工作特征曲线下面积(AUC)评估血清DNMT1、M2BPGi对PLC发生的诊断效能;采用Kaplan-Meier曲线方法和log-rank检验分析血清DNMT1、M2BPGi表达水平与PLC患者预后的关系;通过单因素和多因素Cox回归分析评估影响PLC患者预后的危险因素。结果 PLC患者血清DNMT1、M2BPGi表达水平分别为(2.98±1.57)ng/mL、(3.68±2.07)mg/mL,明显高于对照组的(0.67±0.23)ng/mL、(0.52±0.26)mg/mL(P<0.05)。血清DNMT1、M2BPGi表达与肿瘤直径、肝硬化、淋巴结转移以及血管侵犯等临床病理特征有关(P<0.05)。血清DNMT1、M2BPGi表达水平预测PLC发生的AUC分别为0.708、0.799,灵敏度分别为64.62%、74.72%,特异度分别为71.26%、75.98%。以上指标联合预测PLC发生的AUC为0.923,灵敏度为86.14%,特异度为91.29%。联合预测的AUC明显高于DNMT1(Z=4.615)、M2BPGi(Z=3.382)单独检测(P<0.05)。Kaplan-Meier生存曲线结果显示,血清DNMT1、M2BPGi高表达的PLC患者总生存率(4.35%、6.12%)显著低于血清DNMT1、M2BPGi低表达患者,分别为21.21%、20.00%(P<0.05)。多因素Cox回归分析结果显示,肿瘤直径≥5 cm、有肝硬化、有淋巴结转移、有血管侵犯、DNMT1、M2BPGi高表达均是影响PLC患者预后不良的独立危险因素。结论血清DNMT1、M2BPGi在PLC患者中呈高表达状态,且其表达水平与PLC患者预后不良密切相关,可能成为评估PLC患者预后不良的有效指标。

关键词: 原发性肝癌, DNMT1, M2BPGi, 预后

Abstract: Objective The aim of the present study was to investigate the serum levels of DNA methyltransferase 1 (DNMT1) and Mac-2 binding protein glycosylation isoform (M2BPGi) in patients with primary hepatocellular carcinoma (PLC) and their relationship with the patients′prognosis. Methods Seventy-nine PLC patients who underwent hepatectomy for hepatocellular carcinoma treatment in Tangshan People′s Hospital from May 2020 to May 2021 were retrospectively selected as the study group. Another 37 cases of healthy people for physical examination at the same period of time were selected as the control group. The serum levels of DNMT1 and M2BPGi in subjects of the two study groups were compared and analyzed for their relationship with the clinicopathological characteristics of the PLC patients. The diagnostic efficacy of serum DNMT1 and M2BPGi levels for the occurrence of PLC was assessed using the subjects′ working curves (ROC) and the areas under the curves (AUC). The diagnostic efficacy of serum DNMT1 and M2BPGi levels for the occurrence of PLC was assessed using the Kaplan-Meier curve method. Log-rank test were used to analyze the relationship between the serum DNMT1 and M2BPGi levels and the prognosis of the PLC patients. The risk factors affecting the prognosis of PLC patients were analyzed by univariate and multivariate Cox regression method. Results The levels of serum DNMT1 and M2BPGi in PLC patients of the study group were (2.98±1.57) ng/mL and (3.68±2.07) mg/mL respectively, which were significantly higher than those of (0.67±0.23) ng/mL and (0.52±0.26) mg/mL in the control group (P<0.05). The serum DNMT1 and M2BPGi levels were associated with clinicopathological features such as tumor diameter, the presence of cirrhosis, the presence of lymph node metastasis, and the presence of vascular invasion (P<0.05). The results of the ROC curves showed that serum DNMT1 and M2BPGi levels for predicting PLC occurrence had AUCs of 0.708 and 0.799, sensitivities of 64.62% and 74.72%, and specificities of 71.26% and 75.98%, respectively. The combined prediction of the above indexes for PLC occurrence had an AUC of 0.923, a sensitivity of 86.14%, and a specificity of 91.29%. The AUC of the combined prediction was significantly higher than that of DNMT1 (Z=4.615, P<0.001) and M2BPGi (Z=3.382, P<0.001) used alone (P<0.05). The results of the Kaplan-Meier survival curve analysis showed that the overall survival rate of patients with PLC who had high levels of serum DNMT1 and M2BPGi (4.35% and 6.12%) was significantly lower than that of patients with low levels of serum DNMT1 and M2BPGi (21.21% and 20.00%, P<0.05); the results of multifactorial Cox regression analysis showed that the tumor diameter (≥5 cm), the presence of cirrhosis, the presence of lymph node metastasis, the presence of vascular invasion, and the high expression levels of DNMT1 and M2BPGi were independent risk factors associated with poor prognosis (P<0.05). Conclusion Serum DNMT1 and M2BPGi levels were high in PLC patients, and their serum levels were closely related to the poor prognosis of PLC patients, which may be used as an effective indicator to evaluate the poor prognosis of PLC patients.

Key words: Primary hepatocellular carcinoma, DNMT1, M2BPGi, Prognosis

奚晨阳, 宋晶晶, 马丽丽. 原发性肝癌患者血清DNMT1、M2BPGi的表达及其与预后的关系[J]. 肝脏, 2026, 31(5): 648-652.

XI Chen-yang, SONG Jing-jing, MA Li-li. The serum DNMT1 and M2BPGi levels in patients with primary hepatocellular carcinoma and their relationship with prognosis[J]. Chinese Hepatolgy, 2026, 31(5): 648-652.

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