Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China.
Cancer. 2012 Feb 1;118(3):639-50. doi: 10.1002/cncr.26342. Epub 2011 Aug 18.
The objectives of this study were to identify and validate the diagnostic value of N-glycan markers in colorectal cancer (CRC) and to uncover their underlying molecular mechanism.
In total, 347 individuals, including patients with CRC, patients with colorectal adenoma, and healthy controls, were divided randomly into a training group (n = 287) and retrospective validation groups (n = 60). Serum N-glycan profiling was analyzed by DNA sequencer-assisted/flurophore-assisted carbohydrate electrophoresis (DSA-FACE). Two diagnostic models were constructed based on N-glycan profiling with logistic stepwise regression. The diagnostic performance of each model was assessed further in retrospective, prospective (n = 43), and follow-up (n = 46) cohorts. Lectin blot and reverse transcriptase-polymerase chain reaction were used to analyze the total core-fucosylated residues and molecular expression involved in core-fucosylation modifications in CRC.
Two diagnostic models designated CRCglycoA and CRCglycoB were constructed to differentiate CRC from normal and adenoma, respectively. The areas under the receiver operating characteristic curves (AUC) of both CRCglycoA and CRCglycoB were higher than the AUC of carcinoembryonic antigen (CEA) (CRCglycoA, 0.92 vs 0.81; CRCglycoB, 0.81 vs 0.73). The sensitivity and accuracy of CRCglycoA improved from 21.7% to 25% and from 11.63% to 18% in the training cohort, the retrospective cohort, and the prospective cohorts compared with the sensitivity and accuracy of CEA. The sensitivity of CRCglycoB improved from 20% to 28.23%. Both altered N-glycans, and results from the diagnostic models were reversed after curative surgery. The level of total core fucose residues and fucosyltransferase were decreased significantly in CRC.
The current results indicated that the N-glycan markers based diagnostic models are new, valuable, noninvasive alternatives for identifying CRC. The authors concluded that decreased fucosyltransferase may be responsible for decreased levels of total core-fucosylated modification in both tissues and serum from patients with CRC.
本研究旨在确定并验证结直肠癌（CRC）中 N-聚糖标志物的诊断价值，并揭示其潜在的分子机制。
共纳入 347 名个体，包括 CRC 患者、结直肠腺瘤患者和健康对照者，随机分为训练组（n=287）和回顾性验证组（n=60）。采用 DNA 测序仪辅助/荧光辅助糖电泳（DSA-FACE）分析血清 N-聚糖谱。基于 N-聚糖谱，采用逻辑逐步回归构建两种诊断模型。进一步在回顾性队列、前瞻性队列（n=43）和随访队列（n=46）中评估每个模型的诊断性能。采用凝集素印迹和逆转录-聚合酶链反应分析 CRC 中总核心岩藻糖基化残基和核心岩藻糖基化修饰相关的分子表达。
构建了两种诊断模型 CRCglycoA 和 CRCglycoB，分别用于区分 CRC 与正常和腺瘤。CRCglycoA 和 CRCglycoB 的受试者工作特征曲线下面积（AUC）均高于癌胚抗原（CEA）的 AUC（CRCglycoA，0.92 比 0.81；CRCglycoB，0.81 比 0.73）。与 CEA 相比，在训练组、回顾性队列和前瞻性队列中，CRCglycoA 的灵敏度和准确性从 21.7%提高到 25%和从 11.63%提高到 18%，CRCglycoB 的灵敏度从 20%提高到 28.23%。两种改变的 N-聚糖以及诊断模型的结果在根治性手术后均得到逆转。CRC 中总核心岩藻糖残基和岩藻糖基转移酶的水平显著降低。
目前的结果表明，基于 N-聚糖标志物的诊断模型是识别 CRC 的新的、有价值的非侵入性替代方法。作者得出结论，降低的岩藻糖基转移酶可能是导致 CRC 患者组织和血清中总核心岩藻糖基化修饰水平降低的原因。
