Division of Colon and Rectal Surgery, Department of Surgery, Linko Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Graduate Institute of Clinical Medical Science, Chang Gung University, Taoyuan, Taiwan.
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Biomed J. 2021 Dec;44(6 Suppl 2):S190-S200. doi: 10.1016/j.bj.2020.09.006. Epub 2020 Sep 30.
The immunochemical fecal occult blood test (iFOBT) for colorectal cancer (CRC) screening and the serum carcinoembryonic antigen (CEA) assay for disease detection of CRC is associated with a high false-positive rate and a low detection sensitivity, respectively. There is an unmet need to define additional modalities to complement these assays. Different subsets of circulating tumor cells (CTCs) are present in the peripheral blood of cancer patients. Whether or not CTCs testing supplements these clinical assays and is valuable for patients with CRC was investigated.
CTCs were enriched from pre-operative patients with CRC (n = 109) and the non-cancerous controls (n = 65). CTCs expressing either epithelial cell adhesion molecule (EpCAM) or podoplanin (PDPN, the marker associated with poor cancer prognosis) were defined by immunofluorescence staining and were analyzed alone or in combination with iFOBT or serum CEA.
Patients with early or advanced stage of CRC can be clearly identified and differentiated from the non-cancerous controls (p < 0.001) by EpCAM-CTC or PDPN-CTC count. The sensitivity and specificity of EpCAM-CTCs was 85.3% and 78.5%, respectively, when the cutoff value was 23 EpCAM-CTCs/mL of blood; and the sensitivity and specificity of PDPN-CTCs was 78.0% and 75.4%, respectively, when the cutoff value was 7 PDPN-CTCs/mL of blood. Combined analysis of iFOBT with the EpCAM-CTC and PDPN-CTC count reduced the false-positive rate of iFOBT from 56.3% to 18.8% and 23.4%, respectively. Combined analysis of serum CEA with the EpCAM-CTC and PDPN-CTC count increased the disease detection rate from 30.3% to 89.9% and 86.2%, respectively.
CTC testing could supplement iFOBT to improve CRC screening and supplement serum CEA assay for better disease detection of patients with CRC.
免疫化学粪便潜血试验（iFOBT）用于结直肠癌（CRC）筛查，血清癌胚抗原（CEA）检测用于 CRC 疾病检测，其假阳性率高，检测灵敏度低。因此，需要确定额外的方法来补充这些检测。不同亚群的循环肿瘤细胞（CTC）存在于癌症患者的外周血中。CTC 检测是否可以补充这些临床检测，并对 CRC 患者有价值，对此进行了研究。
从术前 CRC 患者（n=109）和非癌症对照者（n=65）中富集 CTCs。通过免疫荧光染色，定义表达上皮细胞黏附分子（EpCAM）或 podoplanin（PDPN，与不良癌症预后相关的标志物）的 CTCs，并单独或与 iFOBT 或血清 CEA 联合分析。
早期或晚期 CRC 患者可通过 EpCAM-CTC 或 PDPN-CTC 计数与非癌症对照者明显区分（p<0.001）。当截断值为 23 个 EpCAM-CTC/mL 血液时，EpCAM-CTC 的灵敏度和特异性分别为 85.3%和 78.5%；当截断值为 7 个 PDPN-CTC/mL 血液时，PDPN-CTC 的灵敏度和特异性分别为 78.0%和 75.4%。联合分析 iFOBT 与 EpCAM-CTC 和 PDPN-CTC 计数可将 iFOBT 的假阳性率分别降低至 18.8%和 23.4%。联合分析血清 CEA 与 EpCAM-CTC 和 PDPN-CTC 计数可将疾病检出率分别提高至 89.9%和 86.2%。
CTC 检测可补充 iFOBT 以提高 CRC 筛查效果，补充血清 CEA 检测以更好地发现 CRC 患者的疾病。
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