Detection of hepatocellular carcinoma using glycomic analysis.
Detection of hepatocellular carcinoma using glycomic analysis.
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DOI：
10.1158/1078-0432.ccr-07-5261
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发表时间：
2009-03-01
期刊：
影响因子：
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通讯作者：
Novotny MV
中科院分区：
文献类型：
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作者：
Goldman R;Ressom HW;Varghese RS;Goldman L;Bascug G;Loffredo CA;Abdel-Hamid M;Gouda I;Ezzat S;Kyselova Z;Mechref Y;Novotny MV
肝细胞癌（HCC）是美国日益严重的健康问题。目前使用的临床标志物血清甲胎蛋白仅在约60%的HCC患者中升高;因此，预计鉴定其他标志物将对公共卫生产生重大影响。我们研究的目的是定量评估N-聚糖来源于血清糖蛋白作为检测肝癌的替代标志物。我们使用基质辅助激光解吸/电离飞行时间质谱法对202名参与者（73名HCC病例，77名年龄和性别匹配的无癌症对照，52名慢性肝病患者）血清样本中的83种N-聚糖进行定量比较。N-聚糖从血清糖蛋白中酶促释放，并在质谱定量前进行全甲基化。与对照组相比，HCC患者中57种N-聚糖的丰度显著改变。评价的6种单独聚糖用于分离HCC病例与人群对照的灵敏度范围为73%至90%，特异性范围为36%至91%。三种选定的N-聚糖的组合足以在慢性肝病患者的独立验证集中以90%的灵敏度和89%的特异性对HCC进行分类。在调整慢性病毒感染和其他已知协变量后，三种N-聚糖仍与HCC相关，而其他聚糖在慢性病毒感染进展为HCC的早期阶段显著增加。在丙型肝炎病毒感染率高的人群中，一组三种鉴定的N-聚糖足以检测HCC，预测准确率为90%。这些候选标记物的更广泛的临床效用的进一步评价是必要的。
Hepatocellular carcinoma (HCC) represents an increasing health problem in the United States. Serum α-fetoprotein, the currently used clinical marker, is elevated in only ~60% of HCC patients; therefore, the identification of additional markers is expected to have significant public health impact. The objective of our study was to quantitatively assess N-glycans originating from serum glycoproteins as alternative markers for the detection of HCC. We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for quantitative comparison of 83 N-glycans in serum samples of 202 participants (73 HCC cases, 77 age- and gender-matched cancer-free controls, and 52 patients with chronic liver disease). N-glycans were enzymatically released from serum glycoproteins and permethylated before mass spectrometric quantification. The abundance of 57 N-glycans was significantly altered in HCC patients compared with controls. The sensitivity of six individual glycans evaluated for separation of HCC cases from population controls ranged from 73% to 90%, and the specificity ranged from 36% to 91%. A combination of three selected N-glycans was sufficient to classify HCC with 90% sensitivity and 89% specificity in an independent validation set of patients with chronic liver disease. The three N-glycans remained associated with HCC after adjustment for chronic viral infection and other known covariates, whereas the other glycans increased significantly at earlier stages of the progression of chronic viral infection to HCC. A set of three identified N-glycans is sufficient for the detection of HCC with 90% prediction accuracy in a population with high rates of hepatitis C viral infection. Further evaluation of a wider clinical utility of these candidate markers is warranted.