Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west African populations.
Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west African populations.
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DOI：
10.1371/journal.pone.0068381
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Mendy ME
中科院分区：
文献类型：
--
作者：
Fye HK;Wright-Drakesmith C;Kramer HB;Camey S;Nogueira da Costa A;Jeng A;Bah A;Kirk GD;Sharif MI;Ladep NG;Okeke E;Hainaut P;Taylor-Robinson SD;Kessler BM;Mendy ME
肝细胞癌是全球第三大癌症相关死亡原因，通常通过测量血清 AFP 来诊断；性能较差的独立生物标志物。为了改进这一点，我们的研究重点是通过质谱法鉴定的血浆蛋白，以研究和验证对照和 LC 和 HCC 受试者各自蛋白质组中观察到的差异。使用合并表达谱方法对 339 名受试者进行了液相色谱电喷雾电离四极杆飞行时间质谱分析。对四种显着差异表达的蛋白质进行了 ELISA 测定，以验证它们在冈比亚受试者和尼日利亚试点组中的表达谱。使用逻辑回归分析对所得结果进行整理以进行统计多重分析。鉴定出 26 个蛋白质在三个受试者组之间存在差异表达。直接测量四；与对照患者相比，血红素结合蛋白、α-1-抗胰蛋白酶、载脂蛋白 A1 和补体成分 3 证实了它们在 LC 和 HCC 患者中的丰度变化。这些趋势在尼日利亚的试点验证受试者中得到了独立复制。这些蛋白质的统计多重分析表明，在识别肝硬化或癌变方面，其性能与 ALT 相当或更高。这项工作还提出了可达到的敏感性、特异性和 AUC 统计数据大于报告的 AFP 平均值的初步截止值。这些蛋白质的经过验证的表达变化有可能发展成可用于诊断和/或监测 HCC 和 LC 患者的高性能测试。持续表达趋势的识别强化了这四种蛋白质作为肝病背景下进一步研究的有价值候选者的建议。统计组合还提供了一种新颖的分析方法，能够为绩效评估提出明确的界限和组合。
Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance.
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影响因子：
3.7
作者：
Comunale MA;Rodemich-Betesh L;Hafner J;Wang M;Norton P;Di Bisceglie AM;Block T;Mehta A
通讯作者：
Mehta A
影响因子：
13.5
作者：
Kirk, GD;Lesi, OA;Montesano, R
通讯作者：
Montesano, R
影响因子：
29.4
作者：
Daniele, B;Bencivenga, A;Tinessa, V
通讯作者：
Tinessa, V
影响因子：
4.4
作者：
Hsieh, Sen-Yung;He, Jung-Ru;Chiu, Cheng-Tang
通讯作者：
Chiu, Cheng-Tang
影响因子：
3.4
作者：
Fu, Q;Garnham, CP;Van Eyk, JE
通讯作者：
Van Eyk, JE