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癌相关碳水化合物抗原作为肝细胞癌的潜在生物标志物。

Cancer-associated carbohydrate antigens as potential biomarkers for hepatocellular carcinoma.

机构信息

The PhD Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan.

出版信息

PLoS One. 2012;7(7):e39466. doi: 10.1371/journal.pone.0039466. Epub 2012 Jul 13.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common human malignancies. Therefore, developing the early, high-sensitivity diagnostic biomarkers to prevent HCC is urgently needed. Serum a-fetoprotein (AFP), the clinical biomarker in current use, is elevated in only ~60% of patients with HCC; therefore, identification of additional biomarkers is expected to have a significant impact on public health. In this study, we used glycan microarray analysis to explore the potential diagnostic value of several cancer-associated carbohydrate antigens (CACAs) as biomarkers for HCC. We used glycan microarray analysis with 58 different glycan analogs for quantitative comparison of 593 human serum samples (293 HCC samples; 133 chronic hepatitis B virus (HBV) infection samples, 134 chronic hepatitis C virus (HCV) infection samples, and 33 healthy donor samples) to explore the diagnostic possibility of serum antibody changes as biomarkers for HCC. Serum concentrations of anti-disialosyl galactosyl globoside (DSGG), anti-fucosyl GM1 and anti-Gb2 were significantly higher in patients with HCC than in chronic HBV infection individuals not in chronic HCV infection patients. Overall, in our study population, the biomarker candidates DSGG, fucosyl GM1 and Gb2 of CACAs achieved better predictive sensitivity than AFP. We identified potential biomarkers suitable for early detection of HCC. Glycan microarray analysis provides a powerful tool for high-sensitivity and high-throughput detection of serum antibodies against CACAs, which may be valuable serum biomarkers for the early detection of persons at high risk for HCC.

摘要

肝细胞癌(HCC)是最常见的人类恶性肿瘤之一。因此,迫切需要开发早期、高灵敏度的诊断生物标志物来预防 HCC。目前临床使用的生物标志物血清甲胎蛋白(AFP)仅在约 60%的 HCC 患者中升高;因此,预计鉴定其他生物标志物将对公共卫生产生重大影响。在这项研究中,我们使用糖基微阵列分析来探索几种癌症相关碳水化合物抗原(CACAs)作为 HCC 生物标志物的潜在诊断价值。我们使用糖基微阵列分析了 58 种不同的糖类似物,对 593 个人类血清样本(293 个 HCC 样本;133 个慢性乙型肝炎病毒(HBV)感染样本,134 个慢性丙型肝炎病毒(HCV)感染样本和 33 个健康供体样本)进行定量比较,以探讨作为 HCC 生物标志物的血清抗体变化的诊断可能性。与慢性 HBV 感染个体而非慢性 HCV 感染患者相比,HCC 患者的血清中抗二唾液酸半乳糖基神经节苷脂(DSGG)、抗岩藻糖基 GM1 和抗-Gb2 的浓度明显更高。总体而言,在我们的研究人群中,CACAs 的候选生物标志物 DSGG、岩藻糖基 GM1 和 Gb2 的预测敏感性优于 AFP。我们确定了适合 HCC 早期检测的潜在生物标志物。糖基微阵列分析为 CACAs 血清抗体的高灵敏度和高通量检测提供了有力工具,可能是高危 HCC 人群早期检测的有价值的血清生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5bc5/3396621/0a61bf8b34d3/pone.0039466.g001.jpg

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