Liver cancer is the fifth most common cancer with extremely low five year survival rate. Early diagnosis is of great importance for cancer therapy. In this work, stable isotope labeling-based relative quantitative proteomics and parallel reaction monitoring-based target proteomics were combined for cancer biomarker screening and validation. By using this strategy, 70 significantly changed proteins in hepatocellular carcinoma tissues were obtained, among which seven proteins were further validated. The validated proteins contain the clinically used hepatocellular carcinoma ( HCC ) biomarker alpha-fetoprotein ( AFP ) and the reported biomarker candidates Heat shock protein HSP 90-beta ( HSP90 ) , fatty acid-binding protein, epidermal ( FABP5) and alcohol dehydrogenase 4 ( ADH4) , which demonstrated the robustness of the strategy. The proteins identified in this work could be benefit for further HCC biomarker screening and clinical validation. Moreover, this strategy could be further applied to other cancer types.%肝癌是全球第五大恶性肿瘤,其五年生存率极低,及早地发现与诊断对肝癌的临床治疗具有重要意义.通过结合体外稳定同位素标记的蛋白质组学相对定量技术和基于平行反应监测的靶向蛋白质组学定量技术,建立了一种癌症生物标志物的筛选和验证方法.该方法被用于肝癌组织的差异蛋白质筛选和后期验证,共筛选到70个在癌组织中显著变化的蛋白质,并对其中7个蛋白质进行了验证.所验证的蛋白质包括已在临床使用的肝癌标志物甲胎蛋白(AFP)和文献报道的潜在肝癌生物标志物热休克蛋白(HSP90)、脂肪酸结合蛋白5(FABP5)和乙醇脱氢酶4(ADH4),说明了该方法的可靠性.该文所筛选的差异蛋白质可以为肝癌生物标志物研究和临床验证提供参考;该方法还可用于其他癌症样品的差异蛋白质筛选和验证.
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