Leeds Institute of Molecular Medicine, Wellcome Trust Brenner Building, St. James's University Hospital, University of Leeds, Leeds LS9 7TF, UK.
Br J Cancer. 2013 Feb 19;108(3):662-7. doi: 10.1038/bjc.2012.605. Epub 2013 Jan 15.
Colorectal cancer-specific biomarkers have been used as molecular targets for fluorescent intra-operative imaging, targeted PET/MRI, and selective cytotoxic drug delivery yet the selection of biomarkers used is rarely evidence-based. We evaluated sensitivities and specificites of four of the most commonly used markers: carcinoembryonic antigen (CEA), tumour-associated glycoprotein-72 (TAG-72), folate receptor-α (FRα) and Epithelial growth factor receptor (EGFR).
Marker expression was evaluated semi-quantitatively in matched mucosal and colorectal cancer tissues from 280 patients using immunohistochemistry (scores of 0-15). Matched positive and negative lymph nodes from 18 patients were also examined.
Markers were more highly expressed in tumour tissue than in matched normal tissue in 98.8%, 79.0%, 37.1% and 32.8% of cases for CEA, TAG-72, FRα and EGFR, respectively. Carcinoembryonic antigen showed the greatest differential expression, with tumours scoring a mean of 10.8 points higher than normal tissues (95% CI 10.31-11.21, P<0.001). Similarly, CEA showed the greatest differential expression between positive and negative lymph nodes. Receiver operating characteristic analyses showed CEA to have the best sensitivity (93.7%) and specificity (96.1%) for colorectal cancer detection.
Carcinoembryonic antigen has the greatest potential to allow highly specific tumour imaging and drug delivery; future translational research should aim to exploit this.
结直肠癌特异性生物标志物已被用作荧光术中成像、靶向 PET/MRI 和选择性细胞毒性药物递送的分子靶标,但所选择的生物标志物的使用很少基于证据。我们评估了最常用的四种标志物的敏感性和特异性:癌胚抗原(CEA)、肿瘤相关糖蛋白-72(TAG-72)、叶酸受体-α(FRα)和表皮生长因子受体(EGFR)。
使用免疫组织化学(评分 0-15)评估 280 例患者的粘膜和结直肠癌组织中标志物的表达情况。还检查了 18 例患者的匹配阳性和阴性淋巴结。
CEA、TAG-72、FRα 和 EGFR 在肿瘤组织中的表达分别比匹配的正常组织高 98.8%、79.0%、37.1%和 32.8%。癌胚抗原表现出最大的差异表达,肿瘤评分比正常组织高 10.8 分(95%CI 10.31-11.21,P<0.001)。同样,CEA 在阳性和阴性淋巴结之间表现出最大的差异表达。受试者工作特征分析显示 CEA 对结直肠癌检测具有最佳的敏感性(93.7%)和特异性(96.1%)。
癌胚抗原最有可能实现高度特异性的肿瘤成像和药物递送;未来的转化研究应旨在利用这一点。