目的 探讨原发性肝癌患者血清微小核糖核酸（miR）-145、miR-934、甲胎蛋白（AFP）、胸苷激酶1（TK1）水平与临床病理特征及预后的关系。 方法 选取2021年9月至2023年9月康复大学青岛中心医院收治的202例原发性肝癌患者作为肝癌组，同期205例肝硬化患者作为肝硬化组，213例健康体检者作为对照组，其中肝癌组根据术后3个月预后情况分为预后不良组和预后良好组，分别为56例、146例。肝癌患者出院后每3个月随访一次，随访截止时间为2025年9月或死亡。统计所有研究对象的临床资料，比较肝癌组、肝硬化组、对照组、预后不良组、预后良好组及不同临床病理特征原发性肝癌患者血清miR-145、miR-934、AFP、TK1水平，并用受试者工作特征曲线（ROC）分析不同血清指标联合检测对原发性肝癌患者不良预后的预测价值，绘制Kaplan-Meier生存曲线分析不同血清指标表达水平原发性肝癌患者的总生存期。 结果 肝癌组血清miR-145水平明显低于肝硬化组和对照组，miR-934、AFP、TK1水平高于肝硬化组和对照组（P < 0.05），肝硬化组各指标水平介于肝癌组与对照组之间。TNM Ⅲ期、低分化程度原发性肝癌患者血清miR-145水平低于TNM Ⅰ—Ⅱ期、中高分化程度（P < 0.05）。TNM Ⅲ期、低分化程度原发性肝癌患者血清AFP、TK1水平高于TNM Ⅰ—Ⅱ期、中高分化程度（P < 0.05）。TNM Ⅲ期原发性肝癌患者血清miR-934水平高于TNM Ⅰ—Ⅱ期（P < 0.05）。预后不良组血清miR-145水平低于预后良好组，其余3项指标则更高（均P < 0.05）。ROC曲线分析显示，4项指标联合预测不良预后的曲线下面积（AUC）为0.897（95%CI：0.846 ~ 0.935），敏感度为83.93%，特异度为86.99%，优于任一单项指标（P < 0.05）。中位随访时间为35个月。生存分析显示，miR-145高表达组总生存期较长（HR = 0.669，95%CI：0.475 ~ 0.943，P = 0.022），而miR-934、AFP、TK1低表达组总生存期均较长（HR = 0.707，95%CI：0.506 ~ 0.987；HR = 0.700，95%CI：0.501 ~ 0.978；HR = 0.627，95%CI：0.428 ~ 0.917；均P < 0.05）。 结论 miR-145在原发性肝癌患者血清中低表达，miR-934、AFP、TK1在原发性肝癌患者血清中高表达。四者与原发性肝癌患者临床病理特征及不良预后紧密相关，且4项指标联合检测对原发性肝癌患者不良预后具有较高的预测价值，可能为预后评估提供新的生物标志物组合。

Objective To explore the relationship between the levels of serum MicroRNA （miR）-145， miR-934， Alpha-fetoprotein （AFP）， and Thymidine kinase 1 （TK1） in patients with primary liver cancer， as well as their associations with the clinicopathological characteristics and prognosis. Methods From September 2021 to September 2023， 202 cases of primary liver cancer patients admitted to Qingdao Central Hospital， University of Health and Rehabilitation Sciences were selected as the liver cancer group. Meanwhile， 205 patients with liver cirrhosis during the same period were selected as the liver cirrhosis group， and 213 healthy individuals undergoing physical examinations were selected as the control group. Among them， the liver cancer group was further divided into the poor-outcome group and the good-outcome group according to the prognosis 3 months after surgery， with 56 cases in the poor-outcome group and 146 cases in the good-outcome group respectively. After discharge， patients were followed up every three months， and the follow-up period ended in September 2025 or upon the patient's death. The clinical data of all the research subjects were statistically analyzed. The levels of serum miR-145， miR-934， AFP， and TK1 were compared among the liver cancer group， liver cirrhosis group， control group， poor-outcome group， good-outcome group， and patients with primary liver cancer with different clinicopathological characteristics. The predictive value of combined detection of different serum indicators for the poor prognosis of patients with primary liver cancer was analyzed using the receiver operating characteristic curve （ROC）. Additionally， the Kaplan-Meier survival curve was drawn to analyze the overall survival of patients with primary liver cancer at different expression levels of serum indicators. Results The serum miR-145 level in the liver cancer group was significantly lower than those in the liver cirrhosis group and the control group. In contrast， the levels of miR-934， AFP， and TK1 were higher than those in the liver cirrhosis group and the control group （P < 0.05）. Moreover， the levels of each index in the liver cirrhosis group were intermediate between those in the liver cancer group and the control group. The serum miR-145 level in patients with TNM stage Ⅲ and poorly differentiated primary liver cancer was lower than that in patients with TNM stage Ⅰ—Ⅱ and moderately to highly differentiated primary liver cancer （P < 0.05）. The levels of serum AFP and TK1 in patients with TNM stage Ⅲ and poorly differentiated primary liver cancer were higher than those in patients with TNM stage Ⅰ—Ⅱ and moderately to well-differentiated primary liver cancer （P < 0.05）. The serum miR-934 level in patients with TNM stage Ⅲ primary liver cancer was higher than that in patients with TNM stage Ⅰ—Ⅱ primary liver cancer （P < 0.05）. The serum miR-145 level in the poor-outcome group was lower than that in the good-outcome group， whereas the other three indicators were higher （all P < 0.05）. ROC curve analysis demonstrated that the area under the curve （AUC） for the combined prediction of poor prognosis by the four indicators was 0.897 （95%CI： 0.846 ~ 0.935）， with a sensitivity of 83.93% and a specificity of 86.99%， which was superior to any single indicator （P < 0.05）. The median follow-up time was 35 months （range： 3 to 48 months）. Survival analysis indicated that the overall survival period was longer in the miR-145 high-expression group （hazard ratio 0.669， 95%CI： 0.475 ~ 0.943， P = 0.022）， while the overall survival periods were longer in the miR-934， AFP， and TK1 low-expression groups （hazard ratio 0.707， 95%CI： 0.506 ~ 0.987； hazard ratio 0.700， 95%CI： 0.501 ~ 0.978； hazard ratio 0.627， 95%CI： 0.428 ~ 0.917； all P < 0.05）. Conclusions miR-145 exhibited low expression in the serum of patients with primary liver cancer， whereas miR-934， AFP， and TK1 showed high expression in the serum of these patients. These four indicators were closely associated with the clinicopathological characteristics and poor prognosis of patients with primary liver cancer. Furthermore， the combined detection of these four indicators holds high predictive value for the poor prognosis of patients with primary liver cancer and may offer a new biomarker combination for prognosis assessment.