血清唾液酸预测肝内胆管癌微小血管侵犯的临床价值及其机制初探  

Predictive value and related mechanism of serum sialic acid on microvascular invasion in patients with intrahepatic cholangiocarcinoma

作　　者：魏娇 季君 詹月萍 吴琳琳 徐学文 黄晨军 方培丞 肖潇 徐旻[1] 高春芳 Wei Jiao;Ji Jun;Zhan Yueping;Wu Linlin;Xu Xuewen;Huang Chenjun;Fang Peicheng;Xiao Xiao;Xu Min;Gao Chunfang(Clinical Laboratory Medicine Center,Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai200437,China;Department of Laboratory Diagnosis,Shanghai Eastern Hepatobiliary Surgery Hospital,Shanghai200433,China;School of Pharmacy,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院临床检验实验中心,上海200437 [2]上海东方肝胆外科实验诊断科,上海200433 [3]上海中医药大学中药学院,上海201203

出　　处：《中华检验医学杂志》2025年第1期56-64,共9页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金(82372321);上海市卫健委协同创新集群项目(2019CXJQ03);上海申康医院发展中心项目(SHDC2023CRT015)。

摘　　要：目的探讨术前血清唾液酸(SA)评估肝内胆管癌(ICC)患者微小血管侵犯(MVI)的价值。方法收集2020年12月—2024年9月于海军军医大学附属东方肝胆外科医院行手术治疗且病理确诊为ICC的91例患者资料进行回顾性横断面研究,根据MVI病理诊断将患者分为无MVI组(n=41)和MVI组(n=50)。分析患者一般资料及实验室检查指标,采取多因素Logistic回归分析预测MVI的独立危险因素。利用受试者工作特征(ROC)曲线判断上述血清指标对MVI的预测价值。采用点二列相关性分析研究术前SA水平与MVI的关系。通过慢病毒转染构建β-半乳糖苷α2,6-唾液酸转移酶1(ST6GAL1)过表达的ICC细胞株。采用Western blot检测细胞ST6GAL1的蛋白表达情况;实时荧光定量聚合酶链反应检测细胞ST6GAL1的基因表达情况;黑接骨木(SNA)凝集素荧光染色检测细胞α2,6-唾液酸化水平;划痕实验和Transwell实验检测细胞迁移能力;克隆形成实验检测细胞增殖能力。结果与无MVI组比较,MVI组患者纤维蛋白原、天冬氨酸转氨酶、γ-谷氨酰基转移酶、碱性磷酸酶、SA和5′-核苷酸酶(5′-NT)水平较高(P均<0.05)。多因素Logistic回归显示,仅SA是MVI的独立危险因素(OR=1.01,95%CI 1.01~1.02,P=0.023)。SA预测MVI的ROC曲线下面积为0.757(95%CI 0.640~0.870),敏感度67.65%,特异度77.78%。SA与MVI呈正相关(r=0.443,P<0.001)。ST6GAL1过表达的ICC细胞SNA凝集素平均荧光强度增加,细胞表面α2,6-唾液酸化水平明显升高(P均<0.05)。高唾液酸化的ICC细胞克隆形成数量增多(P<0.05),迁移率和迁移细胞数量增加(P<0.05)。结论血清SA是预测ICC患者MVI的独立危险因素。高唾液酸化的ICC细胞恶性程度增加。ObjectiveTo explore the value and related mechanism of preoperative serum sialic acid(SA)on evaluating microvascular invasion(MVI)in patients with intrahepatic cholangiocarcinoma(ICC).MethodsA total of 91 patients who underwent surgical resection and were pathologically diagnosed with ICC from December 2020 to September 2024 at the Oriental Hepatobiliary Surgery Hospital affiliated to the Naval Medical University were included in this retrospective analysis.The patients were divided into non-MVI(41 cases)and MVI groups(50 cases).The general data and laboratory examination indexes were collected and analyzed.Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for predicting MVI.The predictive value of serum indicators for MVI was evaluated by receiver operating characteristic curves.The correlation between MVI and SA was analyzed by point-biserial correlation.ICC cells stably overexpressingβ-galactosideα2,6-sialyltransferase 1(ST6GAL1)were generated through lentiviral transfection.ST6GAL1 protein expression and mRNA expression were detected by Western blot and quantitative real-time polymerase chain reaction,respectively.Sambucus nigra(SNA)lectin fluorescence staining was used to detectα2,6-sialylation levels on cells.Cell migration ability was assessed by wound healing and Transwell assays,and cell proliferation was evaluated by colony formation assays.ResultsCompared with the non-MVI group,patients in the MVI group exhibited significantly higher levels of fibrinogen,aspartate aminotransferase,gamma-glutamyl transferase,alkaline phosphatase,SA and 5′-nucleotidase(5′-NT)(all P<0.05).Multivariate logistic regression analysis revealed that SA(OR=1.01,95%CI 1.01-1.02,P=0.023)was the only independent predictor for MVI.The area under curve of SA in predicting MVI was 0.757(95%CI 0.640-0.870),sensitivity 67.65%,specificity 77.78%.SA was positively correlated with MVI(r=0.443,P<0.001).ICC cells overexpressing ST6GAL1 were featured with increased mean fluores

关 键 词：胆管肿瘤 肝内胆管癌 唾液酸类 微小血管侵犯 危险因素 

分 类 号：R735.8[医药卫生—肿瘤]