Research Department of Surgical Biotechnology, Division of Surgery and Interventional Science, University College London, London, UK.
Department of Surgery, University College London Hospital, London, UK.
Cancer Med. 2022 Aug;11(15):2957-2968. doi: 10.1002/cam4.4664. Epub 2022 Mar 27.
Colorectal cancer (CRC) is the second cause of cancer death worldwide. The role of circulating microvesicles as a screening tool is a novel, yet effective approach that warrants prioritised research.
In a two-gate diagnostic accuracy study, 35 patients with benign colorectal polyps (BCRP) (n = 16) and colorectal cancer (CRC) (n = 19) were compared to 17 age-matched healthy controls. Total annexin-V positive microvesicles and sub-populations positive for selected biomarkers relevant to bowel neoplasm were evaluated in patients' plasma using flow cytometry. Statistical methods including factor analysis utilising two component factors were performed to obtain optimal diagnostic accuracy of microvesicles in identifying patients with colorectal neoplasms.
Total plasma microvesicles, and sub-populations positive for CD31, CD42a, CD31+/CD42a-, EPHB2, ICAM and LGR5 (component factor-1) were able to identify patients with BCRP and CRC with a receiver operator curve (AUC) accuracy of a 100% (95% CI: 100%-100%) and 95% (95% CI: 88%-100%), respectively. To identify patients with BCRP, a cut-off point value of component factor-1761 microvesicles/μl demonstrated a 100% sensitivity, specificity and negative predictive value (NPV) and a 93% positive predictive value (PPV). To identify patients with CRC, a cut-off value of component factor-1 439 microvesicles/μl demonstrated a 100% sensitivity, specificity and NPV and a 65% PPV. CEA+ microvesicles sub-population were significantly (p < 0.02) higher in CRC in comparison to BCRP.
Microvesicles as biomarkers for the early and accurate detection of CRC is a simple and effective tool that yields a potential breakthrough in clinical management.
结直肠癌（CRC）是全球癌症死亡的第二大原因。循环微泡作为一种筛查工具具有新颖性，同时也是一种有效的方法，值得优先研究。
在一项双门诊断准确性研究中，将 35 名患有良性结直肠息肉（BCRP）（n=16）和结直肠癌（CRC）（n=19）的患者与 17 名年龄匹配的健康对照者进行比较。使用流式细胞术评估患者血浆中总膜联蛋白-V 阳性微泡和对肠肿瘤有意义的选定生物标志物阳性的亚群。采用因子分析方法利用两个分量因素进行统计分析，以获得微泡在识别结直肠肿瘤患者方面的最佳诊断准确性。
总血浆微泡和 CD31、CD42a、CD31+/CD42a-、EPHB2、ICAM 和 LGR5 阳性的亚群（分量因素-1）能够识别出患有 BCRP 和 CRC 的患者，其受试者工作特征（ROC）曲线（AUC）准确性为 100%（95%CI：100%-100%）和 95%（95%CI：88%-100%）。为了识别出患有 BCRP 的患者，当分量因素-1 微泡/μl 的截断值为 761 时，其具有 100%的敏感性、特异性和阴性预测值（NPV），阳性预测值（PPV）为 93%。为了识别出患有 CRC 的患者，当分量因素-1 微泡/μl 的截断值为 439 时，其具有 100%的敏感性、特异性和 NPV，PPV 为 65%。与 BCRP 相比，CRC 中 CEA+微泡亚群显著升高（p<0.02）。
作为 CRC 早期和准确检测的生物标志物，微泡是一种简单有效的工具，有望在临床管理方面取得突破。
