血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究

Study on the relationship between serum miR-24-3p, H2AFX and clinical pathological features and postoperative recurrence in liver cancer patients

目的探讨血清微RNA(miR)-24-3p、H2A组蛋白家族成员X(H2AFX)与肝癌患者临床病理特征及术后复发的关系。方法选取2018年3月至2022年3月南通大学附属肿瘤医院收治的108例肝癌初诊患者为研究对象(肝癌组), 另选取同期于本院就诊的86例肝脏良性病变患者作为良性病变组, 行体检的64例健康者为对照组。采用荧光定量PCR法检测并分析各组受试者血清miR-24-3p、H2AFX水平, 对复发和未复发肝癌患者血清miR-24-3p、H2AFX水平进行比较, 对不同血清miR-24-3p、H2AFX水平肝癌患者临床病理特征进行比较, logistic回归分析肝癌患者术后复发的影响因素。结果至随访结束, 108例肝癌患者46例复发。对照组、良性病变组、肝癌组血清miR-24-3p水平分别为1.01±0.23、0.79±0.21、0.55±0.13, 差异有统计学意义(F=125.86, P<0.001), 良性病变组、肝癌组患者血清miR-24-3p水平均低于对照组(均P<0.05), 肝癌组患者血清miR-24-3p水平低于良性病变组(P<0.05);3组血清H2AFX水平分别为1.02±0.25、1.27±0.31、1.59±0.37, 差异有统计学意义(F=65.40, P<0.001), 良性病变组、肝癌组患者血清H2AFX水平均高于对照组(均P<0.05), 肝癌组患者血清H2AFX水平高于良性病变组(P<0.05)。miR-24-3p、H2AFX高水平与低水平肝癌患者TNM分期(χ^(2)=7.85, P=0.005;χ^(2)=6.32, P=0.012)、分化程度(χ^(2)=11.59, P=0.001;χ^(2)=9.92, P=0.002)差异均有统计学意义。与未复发肝癌患者相比, 复发患者血清miR-24-3p水平明显降低(0.44±0.12比0.64±0.14), H2AFX水平明显升高(1.87±0.42比1.38±0.33), 差异均有统计学意义(t=7.79, P<0.001;t=6.79, P<0.001)。单因素分析显示, TNM分期(OR=1.57, 95%CI为1.05~2.35, P=0.029)、分化程度(OR=2.20, 95%CI为1.20~4.02, P=0.011)、miR-24-3p水平(OR=0.66, 95%CI为0.45~0.95, P=0.026)、H2AFX水平(OR=1.73, 95%CI为1.14~2.60, P=0.009)均是肝癌患者术后复发的影响因素;多因素分析显示, TNM分期(OR=2.10, 95%CI为1.14~3.86, P=0.017)、分化程度(OR=1.58, 95%CI为1.12~2.23, P=0.009)、miR-24-3p水平(OR=0.76, 95%CI为0.63~0.92, P=0.005)、H2AFX水平(OR=1.90, 95%CI为1.20~2.99, P=0.006)均是肝癌患者术后复发的独立影响因素。结论不同血清miR-24-3p、H2AFX水平的肝癌患者肿瘤TNM分期、分化程度差异均有统计学意义, 血清miR-24-3p、H2AFX水平是肝癌患者术后复发的影响因素。

Objective To explore the relationship between serum microRNA(miR)-24-3p,H2A histone family member X(H2AFX)and clinical pathological features and postoperative recurrence in liver cancer patients.Methods A total of 108 newly diagnosed liver cancer patients admitted to Tumor Hospital Affiliated to Nantong University from March 2018 to March 2022 were regarded as the liver cancer group.Eighty-six patients with benign liver lesions who visited our hospital during the same period were selected as the benign lesion group,and 64 healthy individuals who underwent physical examinations were selected as the control group.Quantitative real-time PCR method was applied to detect and analyze the levels of serum miR-24-3p and H2AFX mRNA in each group.The serum miR-24-3p and H2AFX levels in patients with recurrent and non-recurrent liver cancer were compared,and the comparison of clinicopathological characteristics of patients with liver cancer with different serum miR-24-3p and H2AFX levels was conducted.Logistic regression was applied to analyze the risk factors affecting postoperative recurrence in liver cancer patients.Results To the end of follow-up,of the 108 patients with liver cancer,46 relapsed.The serum miR-24-3p levels in control group,benign lesion group,and liver cancer group were 1.01±0.23,0.79±0.21 and 0.55±0.13,respectively,with a statistically significant difference(F=125.86,P<0.001),serum miR-24-3p level in benign lesion group and liver cancer group was lower than that in control group(both P<0.05),and serum miR-24-3p level in liver cancer group was lower than that in benign lesion group(P<0.05).The serum H2AFX mRNA levels in control group,benign lesion group,and liver cancer group were 1.02±0.25,1.27±0.31 and 1.59±0.37,respectively,with a statistically significant difference(F=65.40,P<0.001),serum miR-24-3p level in benign lesion group and liver cancer group were higher than that in control group(both P<0.05),and serum miR-24-3p level in liver cancer group was higher than that in benign lesion group(P<0.05).There were statistically significant differences in TNM stage(χ^(2)=7.85,P=0.005;χ^(2)=6.32,P=0.012)and differentiation degree(χ^(2)=11.59,P=0.001;χ^(2)=9.92,P=0.002)between patients with high and low level of miR-24-3p and H2AFX.Compared with the non-relapsed patients,the serum miR-24-3p level was significantly lower(0.44±0.12 vs.0.64±0.14)and the H2AFX level was significantly higher(1.87±0.42 vs.1.38±0.33)among the relapsed patients,with statistically significant differences(t=7.79,P<0.001;t=6.79,P<0.001).Univariate analysis showed that TNM stage(OR=1.57,95%CI:1.05-2.35,P=0.029),differentiation degree(OR=2.20,95%CI:1.20-4.02,P=0.011),miR-24-3p level(OR=0.66,95%CI:0.45-0.95,P=0.026),H2AFX level(OR=1.73,95%CI:1.14-2.60,P=0.009)were all influential factors for postoperative recurrence in liver cancer patients.Multifactorial analysis showed that TNM stage(OR=2.10,95%CI:1.14-3.86,P=0.017),differentiation degree(OR=1.58,95%CI:1.12-2.23,P=0.009),miR-24-3p level(OR=0.76,95%CI:0.63-0.92,P=0.005),H2AFX level(OR=1.90,95%CI:1.20-2.99,P=0.006)were the independent influencing factors of postoperative recurrence in liver cancer patients.Conclusion There are statistically significant differences in tumor TNM stage and differentiation degree among liver cancer patients with different serum miR-24-3p and H2AFX levels,and serum miR-24-3p and H2AFX levels are the influencing factors for postoperative recurrence in liver cancer patients.