南方医科大学学报

南方医科大学学报 ›› 2023, Vol. 43 ›› Issue (11): 1874-1880.doi: 10.12122/j.issn.1673-4254.2023.11.06

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粪便蛋白Luminex液相芯片检测系统构建及其对结直肠肿瘤早期诊断的价值

李 静，殷丽霞，张 敏，夏勇生，左芦根，刘牧林，胡建国   

  1. 蚌埠医学院第一附属医院检验科，胃肠外科，炎症相关性疾病基础与转化研究安徽省重点实验室，安徽 蚌埠 233000
  • 出版日期:2023-11-20 发布日期:2023-12-08

Construction of a fecal protein Luminex liquid chip detection system for early diagnosis of colorectal tumors

LI Jing, YIN Lixia, ZHANG Min, XIA Yongsheng, ZUO Lugen, LIU Mulin, HU Jianguo   

  1. Clinical Laboratory, Department of Gastrointestinal Surgery, Key Laboratory of Basic and Translational Research of Inflammation-Related Diseases, First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
  • Online:2023-11-20 Published:2023-12-08

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摘要： 目的 基于Luminex液相芯片检测系统构建粪便人源性蛋白诊断体系，并评估其对结直肠肿瘤的早期诊断价值。方法 收集2021年1月~2023年1月蚌埠医学院第一附属医院收治的结直肠癌（CRC）患者70例为CRC组、结直肠腺瘤（CRA）患者42例为CRA组，以及同期健康对照（HC）受试者38例为HC组。收集各组受试者粪便，使用Tris-Hcl缓冲液提取粪便总蛋白，通过Luminex液相芯片检测技术分析3组受试者粪便中基质金属蛋白酶-9（MMP-9）、人源性视黄醇结合蛋白4（RBP4）、甲壳素酶-3样蛋白1（CHI3L1）和补体成分3a（C3a）的水平差异；收集受试者外周血，分离血清检测癌胚抗原（CEA）和糖类抗原19-9（CA19-9）的水平；使用受试者工作曲线（ROC）分析MMP-9、RBP4、CHI3L1和C3a联合以及CEA和CA19-9联合对CRC、CRA、CRC和CRA的诊断效能，并比较两种组合诊断效能的差异。结果 CRC组患者粪便中MMP-9、RBP4、CHI3L1和C3a水平均显著高于HC组（P<0.05），CRC组粪便中MMP-9和CHI3L1水平显著高于CRA组（P<0.05），但是RBP4和C3a在CRC和CRA组间并无显著性差异（P>0.05）；另外，CRC患者外周血中CEA和CA19-9水平均显著高于HC组和CRA组（P<0.05），但是CRA组和HC组之间无显著性差异（P>0.05）。ROC曲线分析显示，MMP-9、RBP4、CHI3L1和C3a联合诊断CRC的灵敏度为91.4%，特异度为100.0%，联合诊断CRA的灵敏度为81.0%，特异度为89.5%，联合诊断CRC和CRA的灵敏度为83.9%，特异度为97.4%。Z检验比较分析显示，粪便蛋白MMP-9、RBP4、CHI3L1和C3a联合诊断CRC，CRA以及CRA和CRC的效能显著优于外周血肿瘤标志物CEA和CA19-9（P<0.05）。结论 Luminex液相芯片检测粪便人源性蛋白RBP4、MMP-9、CHI3L1、C3a对结直肠肿瘤早期诊断具有价值且优于外周血肿瘤标志物CEA和CA19-9，具有较高的临床应用推广意义。

关键词: 结直肠肿瘤；早期诊断；粪便蛋白；Luminex液相芯片技术

Abstract: Objective To construct a stool- based human protein diagnostic system using the Luminex liquid chip system for early diagnosis of colorectal tumors. Methods From January, 2021 to January, 2023, 70 patients with colorectal cancer (CRC), 42 patients with colorectal adenoma (CRA), and 38 healthy individuals were recruited from our hospital for detecting fecal protein levels of matrix metalloproteinase-9 (MMP-9), retinol- binding protein 4 (RBP4), chitinase-3-like protein 1 (CHI3L1), and complement component 3a (C3a) using Luminex liquid chip technology and serum levels of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) using chemiluminescence assay. Receiver-operating characteristic (ROC) curve analysis was used for assessing the diagnostic efficacy of the combination of MMP- 9, RBP4, CHI3L1 and C3a and the combination of CEA and CA19-9 for colorectal tumors. Results The fecal contents of MMP-9, RBP4, CHI3L1, and C3a were significantly higher in CRC patients than in healthy individuals (P<0.05). Fecal MMP-9 and CHI3L1 levels were significantly higher in CRC than in CRA patients (P<0.05), but RBP4 and C3a levels did not differ significantly (P>0.05). CRC patients had significantly higher serum CEA and CA19- 9 levels than healthy individuals and CRA patients (P<0.05), but the differences were not significant between the latter two groups (P>0.05). ROC analysis showed that the sensitivity and specificity of the combination of MMP-9, RBP4, CHI3L1, and C3a was 91.4% and 100.0%, for diagnosing CRC, 81.0% and 89.5% for diagnosing CRA, and 83.9% and 97.4% for a combined diagnosis of CRC and CRA, respectively. Z-test analysis indicated that fecal MMP-9, RBP4, CHI3L1, and C3a contents had a greater diagnostic efficacy than serum tumor markers CEA and CA19-9 for a combined diagnosis of colorectal tumors (P<0.05). Conclusion The Luminex liquid chip detection system for detecting decal RBP4, MMP-9, CHI3L1, and C3a provides an effective means for early diagnosis of colorectal tumors with a greater diagnostic efficacy than serum CEA and CA19-9 levels.

Key words: colorectal cancer; early diagnosis; fecal protein; Luminex liquid chip technology