Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma.
Identification of serologic biomarkers for predicting microvascular invasion in hepatocellular carcinoma.
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预测肝细胞癌微血管侵袭的血清学生物标志物的鉴定
DOI：
10.18632/oncotarget.7649
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发表时间：
2016-03-29
期刊：
影响因子：
--
通讯作者：
Li JT
中科院分区：
文献类型：
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作者：
Yu YQ;Wang L;Jin Y;Zhou JL;Geng YH;Jin X;Zhang XX;Yang JJ;Qian CM;Zhou DE;Liu DR;Peng SY;Luo Y;Zheng L;Li JT
肝细胞癌（HCC）的微血管浸润（MVI）是根治性手术治疗后早期复发和生存率低的主要危险因素。但MVI的诊断只能依靠手术切除后的病理检查。本研究的目的是确定术前预测MVI的血清学生物标志物，以帮助促进治疗决策。我们使用血清蛋白质组学方法来鉴定特异性地在来自MVI（+）患者或来自MVI（-）患者的血清中诱导相应抗体应答的抗原。随后通过质谱鉴定了6种抗原，分别为HSP 70、HSP 90、α-烯醇化酶（Eno-1）、膜联蛋白A2、谷胱甘肽合成酶和β-肌动蛋白。通过ELISA测量血清中对应于这六种抗原中的四种的抗体滴度，并在35名MVI（+）患者和26名MVI（-）患者之间进行比较。MVI（-）患者的抗HSP 70抗体滴度显著高于MVI（+）患者; MVI（-）患者的抗Eno-1抗体滴度显著低于MVI（+）患者。结果与其他临床病理因素一起进行多变量分析，表明血清中HSP 70和Eno-1抗体是预测HCC手术切除前MVI的潜在生物标志物。这些生物标志物应作为潜在的治疗靶点进一步研究。
Microvascular invasion (MVI) of hepatocellular carcinoma (HCC) is a major risk factor for early recurrence and poor survival after curative surgical therapies. However, MVI can only be diagnosed by pathological examination following resection. The aim of this study is to identify serologic biomarkers for predicting MVI preoperatively to help facilitate treatment decisions. We used the sero-proteomic approach to identify antigens that induce corresponding antibody responses either specifically in the serum from MVI (+) patients or from MVI (−) patients. Six antigens were subsequently identified as HSP 70, HSP 90, alpha-enolase (Eno-1), Annexin A2, glutathione synthetase and beta-actin by mass spectrometry. The antibodies titers in sera corresponding to four of these six antigens were measured by ELISA and compared between 35 MVI (+) patients and 26 MVI (−) patients. The titers of anti-HSP 70 antibodies were significantly higher in MVI (−) patients than those in MVI (+) patients; and the titers of anti-Eno-1 antibodies were significantly lower in MVI (−) patients than those in MVI (+) patients. The results were subjected to multivariate analysis together with other clinicopathologic factors, suggesting that antibodies against HSP 70 and Eno-1 in sera are potential biomarkers for predicting MVI in HCC prior to surgical resection. These biomarkers should be further investigated as potential therapeutic targets.