血浆胆汁酸在肝肿瘤中的差异分析及应用价值

Abstract

目的 分析原发性肝癌与转移性肝癌患者血浆胆汁酸水平及其与临床指标的相关性，并评估其联合AFP对于原发性肝癌的诊断价值。 方法 纳入2020年8月—2021年9月于上海中医药大学附属曙光医院就诊且具有组织病理学及影像学明确的75例原发性肝癌患者及79例转移性肝癌患者，采集外周血并分别分离血清及血浆，比色法及色谱法检测生化指标，电化学发光免疫分析法检测肿瘤标志物水平，高效液相色谱-串联质谱法检测胆汁酸含量。符合正态分布的计量资料两组间比较采用成组t检验，不符合正态分布的计量资料两组间比较采用Mann-Whitney U检验。相关性检验采用Spearman相关分析。临床诊断效能采用受试者工作特征曲线 (ROC曲线) 评估。 结果 原发性肝癌组患者TC、TG、LDL-C及载脂蛋白 (Apo) B显著低于转移性肝癌组患者，差异均具有统计学意义 (U值分别为1 598、1 255、909、889，P值均<0.05) 。原发性肝癌组患者AFP显著高于转移性肝癌组患者，癌胚抗原 (CEA) 显著低于转移性肝癌组患者，差异均具有统计学意义 (U值分别为1 873、926，P值均<0.05) 。原发性肝癌组患者总胆汁酸 (TBA) 、胆酸 (CA) 、鹅脱氧胆酸 (CDCA) 、熊脱氧胆酸 (UDCA) 、牛磺胆酸 (TCA) 、牛磺鹅脱氧胆酸 (TCDCA) 、甘氨胆酸 (GCA) 、甘氨鹅脱氧胆酸 (GCDCA) 、牛磺熊脱氧胆酸 (TUDCA) 、甘氨熊脱氧胆酸 (GUDCA) 均显著高于转移性肝癌患者，脱氧胆酸 (DCA) 显著低于转移性肝癌患者，差异均具有统计学意义 (P值均<0.05) 。总人群中TBA、CDCA、GCA、GCDCA、GUDCA、TCA、TCDCA及TUDCA含量与AFP水平呈显著正相关 (P值均<0.05) 。原发性肝癌患者中GCA、TCA、TCDCA及TUDCA含量与AFP水平呈显著正相关 (P值均<0.05) 。AFP+TCA+GCA+TCDCA联合检测的AUC为0.822 (95%CI：0.746～0.898，P<0.000 1) ，效能最高。 结论 原发性肝癌与转移性肝癌患者血浆胆汁酸含量具有显著差异，差异性胆汁酸与肝损伤及AFP升高密切相关，联合AFP对原发性肝癌具有更优的临床诊断价值。

Alternate abstract:

Objective To investigate the levels of plasma bile acids (BA) in patients with primary liver cancer (PLC) or metastatic liver cancer (MLC) and their correlation with clinical indicators, as well as the value of plasma BAs combined with alpha-fetoprotein (AFP) in the diagnosis of PLC. Methods This study was conducted among 75 patients with PLC and 79 patients with MLC who attended Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from August 2020 to September 2021 and had a confirmed diagnosis based on histopathological and imaging findings. Peripheral blood samples were collected from all patients, and serum and plasma were separated. Colorimetry and chromatography were used to measure biochemical parameters; electrochemiluminescence immunoassay was used to measure the levels of tumor markers; liquid chromatography-tandem mass spectrometry was used to measure the content of BA. The t-test was used for comparison of normally distributed continuous data, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data; the Spearman’s coefficient was used for correlation analysis; the receiver operating characteristic (ROC) curve was used to evaluate clinical diagnostic efficacy. Results The PLC group had significantly lower levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, and apolipoprotein B than the MLC group (U=1 598, 1 255, 909, and 889, all P<0.05). Compared with the MLC group, the PLC group had a significantly higher level of AFP and a significantly lower level of carcinoembryonic antigen (U=1 873 and 926, both P<0.05). Compared with the MLC group, the PLC group had significantly higher levels of TBA, CA, CDCA, UDCA, TCA, TCDCA, GCA, GCDCA, TUDCA, and GUDCA and a significantly lower level of DCA (all P<0.05). In the total population, the levels of TBA, CDCA, GCA, GCDCA, GUDCA, TCA, TCDCA, and TUDCA were significantly positively correlated with the level of AFP (all P<0.05). In the patients with PLC, the levels of GCA, TCA, TCDCA, and TUDCA were significantly positively correlated with the level of AFP (all P<0.05). Combined measurement of AFP+TCA+GCA+TCDCA had an area under the ROC curve of 0.822 (95% confidence interval: 0.746‍ ‍- ‍0.898, P<0.000 1), suggesting that it had the highest diagnostic efficacy. Conclusion There are significant differences in the levels of plasma BA between the patients with PLC and those with MLC, and the differentially expressed BAs are closely associated with liver function impairment and the increase in AFP. BAs combined with AFP has a better clinical value in the diagnosis of PLC.