Objective: To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer. Methods: 393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests. Results: 367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant (χ (2) = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant (χ (2) = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant (χ (2) = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion: In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.
目的： 研究血浆甲基化SEPT9基因（mSEPT9）在原发性肝癌患者中的表达及临床意义。 方法： 选取2016年5月至2018年10月在西安就诊393例患者资料，其中原发性肝癌组75例、肝硬化组50例、健康对照组268例。应用聚合酶链式反应荧光探针法检测3组外周血浆mSEPT9表达阳性率，并分析其与肝癌临床特征的相关性，同时与电化学发光法检测的甲胎蛋白阳性率进行比较。采用χ(2)检验或连续性校正的χ(2)检验进行统计学分析。 结果： 实际有效样本数为367例。肝癌组64例，肝硬化组42例，健康对照组261例，其中获得肝癌病理组织者34例。血浆mSEPT9阳性率在肝癌组明显高于肝硬化与健康对照组[分别为76.6%（49/64）、35.7%（15/42）、3.8%（10/261）]，差异均有统计学意义（χ(2) = 176.017，P <0.001）。肝癌患者血浆mSEPT9检测灵敏度（76.6%）明显优于甲胎蛋白（54.7%），差异具有统计学意义（χ(2) = 6.788，P < 0.01）。血浆mSEPT9联合甲胎蛋白检测较其单一检测灵敏度及特异度均明显提高（分别为89.7%、特异度96.3%）。肝癌患者年龄≥50岁、临床分期Ⅱ期以上及病理示中低分化者血浆mSEPT9阳性表达较高，差异均有统计学意义（χ(2) = 6.41、9.279、6.332，P值均<0.05）。随访期间血浆mSEPT9表达阳性的肝癌患者生存时间明显短于阴性者[分别为（310±26）、（487±59），差异具有统计学意义（Log Rank，P = 0.039）]。 结论： 血浆mSEPT9检测在我国肝癌患者中的阳性率高于甲胎蛋白，且与年龄及临床分期、组织分化程度相关，并有一定生存预测价值，故检测该基因在原发性肝癌患者无创诊断及预后评估中具有重要的临床意义，有潜在的临床应用价值。.
Keywords: Clinical significance; Diagnosis; Methylation; Primary liver cancer; SEPT9 DNA.