A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values.

A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values.
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一组新颖的生物标志物,可区分小型分化良好的 HCC 与发育不良结节及结果值

DOI:
10.1186/1471-2407-13-161
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发表时间:
2013-03-27
期刊:
影响因子:
3.8
通讯作者:
Wu MC
Wu MC
中科院分区:
医学2区
文献类型:
--
作者:
Jin GZ;Dong H;Yu WL;Li Y;Lu XY;Yu H;Xian ZH;Dong W;Liu YK;Cong WM;Wu MC

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高度发育不良结节(HGDN)和高分化肝细胞癌(WDHCC)的鉴别诊断对有经验的肝脏临床医生、放射科医生和肝脏病理学家来说是一项挑战。采用免疫组织化学方法检测低度发育不良结节(LGDN)、HGDN和WDHCC中氨基酰基酶-1(ACY1)、隔离体-1(SQSTM1)和Glypcan-3(GPC3)的表达。用Logistic回归模型(HGDN = 2 1;WHCHC = 32)研究这3种标志物单独及联合应用对HGDN和WHPCN的鉴别诊断性能,并在独立测试集(HGDN n = 2 1;WHSCN n = 2 4)中进行验证。在一组独立的500名患者中,通过单变量和多变量分析评估了术后总存活率和复发时间。ACY1、SQSTM1和GPC3在各组均有不同程度的表达。ACY1、 + 、SQSTM1、 + 、GPC3组合对肝硬变和肾性糖尿病的鉴别诊断的敏感性和特异度分别为93.8%和95.2%,均高于三种双标记组合中的任一种。在独立的测试集中进一步验证了四种诊断模型的有效性,并观察到了相应的良好的灵敏度和特异度。有趣的是,GPC3在肝细胞癌组织中的表达和血清甲胎蛋白(α)被发现是总生存期和复发时间的独立预测因子。ACY1、 + 、SQSTM1HGPC3组合可能是一种有价值的免疫组织化学标记物,可用于鉴别 + 和HGDN。同时,低GPC3染色结合血清AFP阳性可能在预测术后不良预后和高肿瘤复发风险方面具有实用价值。
Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists. The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients. ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence. ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk.
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