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| 结直肠癌肝转移患者的血浆胆汁酸谱特征及临床价值 |
| 贾茹1,张平平1,袁苑2,王炎1,冯琴3,4,5,6* |
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(1. 上海中医药大学附属曙光医院肿瘤科, 上海 201203;
2. 上海中医药大学中西医结合学院, 上海 201203;
3. 上海中医药大学肝病研究所, 上海 201203;
4. 上海市中医临床重点实验室, 上海 201203;
5. 上海中医药大学肝肾疾病病证教育部重点实验室, 上海 201203
6. 上海中医药大学附属曙光医院科技实验中心, 上海 201203
*通信作者) |
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| 摘要: |
| 目的 分析不同转移情况结直肠癌患者血浆胆汁酸含量及胆汁酸谱分布的差异，并评估血浆胆汁酸含量比值联合肿瘤标志物对结直肠癌肝转移的诊断价值。方法 纳入2021年4月至2022年1月于上海中医药大学附属曙光医院就诊的结直肠腺癌肝转移或无转移患者163例，其中无转移组82例、肝转移组81例。收集患者的临床资料，用Karnofsky功能状态（KPS）评分评估生存质量；收集患者外周血样本，检测总胆汁酸及肿瘤标志物［癌胚抗原（CEA）和糖类抗原125（CA125）］水平，用高效液相色谱-串联质谱法检测血浆中15种胆汁酸的含量。分析两组患者胆汁酸含量及胆汁酸谱分布的差异，并绘制ROC曲线分析胆汁酸含量比值联合肿瘤标志物对结直肠癌肝转移的临床诊断效能。结果 两组结直肠癌患者年龄、性别、肿瘤位置、病理分化程度、KPS评分差异无统计学意义（均P＞0.05）。肝转移组患者总胆汁酸、CEA、CA125均较无转移组患者升高（均P＜0.001），血浆胆汁酸谱中甘氨胆酸、脱氧胆酸、牛磺脱氧胆酸、甘氨脱氧胆酸、甘氨熊脱氧胆酸、石胆酸和甘氨石胆酸含量均较无转移组患者升高（均P＜0.05），血浆次级胆汁酸含量高于无转移组患者（P＜0.001），次级胆汁酸与初级胆汁酸含量比值高于无转移组患者（P＜0.001）。次级胆汁酸与初级胆汁酸含量比值联合CEA、CA125诊断结直肠癌肝转移的灵敏度为71.60%，特异度为80.49%，AUC为0.820（95% CI 0.754～0.885，P＜0.001）。结论 结直肠癌肝转移患者血浆胆汁酸含量升高，胆汁酸谱异于无转移患者；次级胆汁酸与初级胆汁酸含量比值联合CEA、CA125对结直肠癌肝转移有较高的诊断价值。 |
| 关键词: 结直肠肿瘤 肝转移 胆汁酸 次级胆汁酸 诊断标志物 |
| DOI：10.16781/j.CN31-2187/R.20240121 |
| 投稿时间：2024-02-21修订日期：2024-04-18 |
| 基金项目:国家自然科学基金（82104619），上海市卫生健康委员会卫生行业临床研究专项（20214Y0455），上海中医药大学预算内项目（2021LK105）. |
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| Characteristic and clinical value of plasma bile acid profile in patients with colorectal cancer liver metastasis |
| JIA Ru1,ZHANG Pingping1,YUAN Yuan2,WANG Yan1,FENG Qin*3,4,5,6* |
(1. Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
2. School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
3. Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China;
4. Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai 201203, China;
5. Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai 201203, China;
6. Central Laboratory, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
* Corresponding author) |
| Abstract: |
| Objective To analyze the differences in plasma bile acid (BA) concentrations and BA profile in colorectal cancer patients with varying metastatic conditions, and to evaluate the clinical value of plasma BA ratio combined with tumor markers in diagnosing colorectal cancer liver metastasis (CRC-LM). Methods A total of 163 patients diagnosed with colorectal cancer between Apr. 2021 and Jan. 2022 were enrolled from Shuguang Hospital of Shanghai University of Traditional Chinese Medicine. They were categorized into 2 groups: non-metastatic group (CRC-NM group, n＝82) and CRC-LM group (n＝81). Clinical data and peripheral blood samples were collected from all the participants, the quality of life was evaluated using Karnofsky performance status (KPS) score, the levels of total bile acid (TBA) and tumor markers (carcinoembryonic antigen［CEA］ and carbohydrate antigen 125［CA125］) were examined, and the plasma concentrations of 15 BAs were detected using high-performance liquid chromatography/tandem mass spectrometry. The BA concentrations and BA profile were compared between the 2 groups. Additionally, receiver operating characteristic curve was generated to evaluate the efficacy of the BA ratio combined with tumor markers in diagnosing CRC-LM. Results No significant difference was found in age, gender, tumor location, degree of pathological differentiation, or KPS score between the 2 groups (all P＞0.05). Patients with CRC-LM had significantly higher concentrations of TBA, CEA and CA125 compared to those without metastasis (all P＜0.001). Additionally, the concentrations of glycocholic acid, deoxycholic acid, taurodeoxycholic acid, glycodeoxycholic acid, glycoursodeoxycholic acid, lithocholic acid and glycolithocholic acid in patients with CRC-LM were significantly higher compared to patients without metastasis (all P＜0.05). Furthermore, the plasma concentration of secondary bile acid (SBA) in CRC-LM patients was significantly higher than that in non-metastatic patients (P＜0.001), and the ratio of SBA to primary bile acid (PBA) was also significantly higher in CRC-LM patients (P＜0.001). Combination of SBA/PBA ratio with CEA and CA125 yielded a sensitivity of 71.60%, a specificity of 80.49%, and an area under curve of 0.820 (95% confidence interval 0.754 to 0.885, P＜0.001). Conclusion The plasma BA concentration is elevated in patients with CRC-LM, and the BA profile is notably different from that of patients without metastasis. The SBA/PBA ratio combined with CEA and CA125 demonstrates a great value for diagnosing CRC-LM. |
| Key words: colorectal neoplasms liver metastasis bile acid secondary bile acid diagnostic marker |
