TRF is a glycoprotein mainly secreted by hepatocytes, The aim of this study was to explore the diagnostic value of aberrant glycosylated serum transferrin (TRF) especially containing multi-antennary glycans in hepatocellular carcinoma (HCC).A total of 581 subjects including HCC patients, liver cirrhosis (LC) patients, chronic hepatitis (CHB) patients and healthy controls (HC) were recruited. All the subjects were randomly assigned to training group (n = 411) and validation group (n = 170). We firstly analyzed the serum protein N-glycome profiling of HCC, LC, and HC by DNA sequencer–assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) technology. We established a lectin-antibody sandwich ELISA (Lectin-ELISA) method to detect multi-antennary glycans-contained TRF (DSA-TRF) in serum, in which Datura stramonium Agglutinin (DSA) was used for specific recognition. Levels of serum DSA-TRF and TRF were analyzed respectively. The diagnostic efficacies of DSA-TRF and TRF of differentiating HCC patients from CHB, LC patients and HC within the training group were evaluated using receiver operating characteristic (ROC) curve and tested in the validation group.The result found that in training group, serum TRF and DSA-TRF levels differed significantly between HCC (1.86 ± 0.50, g/L, 0.285 ± 0.06), CHB + LC (2.39 ± 0.74, g/L, 0.189 ± 0.07) and HC (1.92 ± 0.69, g/L, 0.249 ± 0.09) (HCC vs. CHB + LC, P < 0.001; HCC vs. HC, P < 0.001; CHB + LC vs. HC, P < 0.001). The area under the ROC curve (AUC) of DSA-TRF was significantly superior to AFP (0.880, 95%CI: 0.834–0.925 vs. 0.776, 95%CI: 0.725–0.827, P = 0.003) in differentiating HCC from CHB + LC. The AUC of diagnostic model GlycoTRF1 (0.981, 95%CI: 0.969–0.993) was higher than DSA-TRF and AFP alone (P<0.001) in differentiating HCC from CHB + LC, which was verified in validation group.The results indicated that the serum DSA-TRF might serve as a potential glycan biomarker for distinguishing HCC from CHB and LC.

中文翻译：

---

血清DSA-TRF在肝细胞癌中的诊断价值。

TRF是一种主要由肝细胞分泌的糖蛋白，本研究的目的是探讨异常糖基化血清转铁蛋白（TRF）尤其是含有多天线聚糖的抗体在肝细胞癌（HCC）中的诊断价值。共有581名受试者，包括HCC患者，招募了肝硬化（LC）患者，慢性肝炎（CHB）患者和健康对照（HC）。所有受试者均随机分为训练组（n  = 411）和验证组（n = 170）。我们首先通过DNA测序仪辅助的荧光团辅助碳水化合物电泳（DSA-FACE）技术分析了HCC，LC和HC的血清蛋白N-糖蛋白谱。我们建立了一种凝集素抗体夹心ELISA（Lectin-ELISA）方法来检测血清中多天线含糖TRF（DSA-TRF），其中曼陀罗粘质凝集素（DSA）用于特异性识别。分别分析血清DSA-TRF和TRF的水平。使用受试者工作特征曲线（ROC）评估训练组中HCC患者与CHB，LC患者和HC的DSA-TRF和TRF的诊断效率，并在验证组中进行测试。结果发现，在训练组中，血清HCC（1.86±0.50，g / L，0.285±0.06），CHB + LC（2.39±0.74，g / L，0.189±0.07）和HC（1.92±0.69，g / L，0.249±0.09）（HCC vs.CHB + LC，P <0.001; HCC vs.HC，P <0.001; CHB + LC vs.HC ，P <0.001）。在区分HCC和CHB +方面，DSA-TRF的ROC曲线下面积（AUC）明显优于AFP（0.880，95％CI：0.834-0.925 vs. 0.776，95％CI：0.725-0.827，P = 0.003） LC。诊断模型GlycoTRF1的AUC（0.981，95％CI：0.969–0.993）在将HCC与CHB + LC区分方面高于单独的DSA-TRF和AFP（P <0.001），这在验证组中得到了证实。结果表明：血清DSA-TRF可能作为区分HCC与CHB和LC的潜在聚糖生物标志物。在区分HCC和CHB +方面，DSA-TRF的ROC曲线下面积（AUC）明显优于AFP（0.880，95％CI：0.834-0.925 vs. 0.776，95％CI：0.725-0.827，P = 0.003） LC。诊断模型GlycoTRF1的AUC（0.981，95％CI：0.969–0.993）在将HCC与CHB + LC鉴别中高于单独的DSA-TRF和AFP（P <0.001），这在验证组中得到了证实。结果表明：血清DSA-TRF可能作为区分HCC与CHB和LC的潜在聚糖生物标志物。在区分HCC和CHB +方面，DSA-TRF的ROC曲线下面积（AUC）明显优于AFP（0.880，95％CI：0.834-0.925 vs. 0.776，95％CI：0.725-0.827，P = 0.003） LC。诊断模型GlycoTRF1的AUC（0.981，95％CI：0.969–0.993）在将HCC与CHB + LC区分方面高于单独的DSA-TRF和AFP（P <0.001），这在验证组中得到了证实。结果表明：血清DSA-TRF可能作为区分HCC与CHB和LC的潜在聚糖生物标志物。