LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort.
LC-MS based serum metabolomics for identification of hepatocellular carcinoma biomarkers in Egyptian cohort.
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DOI：
10.1021/pr300673x
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发表时间：
2012-12-07
影响因子：
4.4
通讯作者：
Ressom HW
中科院分区：
文献类型：
--
作者：
Xiao JF;Varghese RS;Zhou B;Nezami Ranjbar MR;Zhao Y;Tsai TH;Di Poto C;Wang J;Goerlitz D;Luo Y;Cheema AK;Sarhan N;Soliman H;Tadesse MG;Ziada DH;Ressom HW
尽管肝细胞癌（HCC）已被不断研究，其症状也众所周知，但这种疾病的早期诊断仍然很困难，诊断后的生存率通常很低（3-5%）。早期准确检测肝硬化患者血清代谢变化，有助于改善HCC预后，更好地了解其分子水平的机制，从而为患者提供及时的治疗。在这项研究中，我们使用超高效液相色谱-四极杆飞行时间质谱联用（UPLC-QTOF MS）比较了40例HCC患者和49例埃及肝硬化患者血清中的代谢物水平。在数据预处理之后，通过统计方法选择与HCC病例和肝硬化对照最相关的离子。这些离子的推定代谢物鉴定是通过基于质量的数据库搜索获得的。通过将其MS/MS碎片模式和保留时间与正品化合物的碎片模式和保留时间进行比较，验证了一些推定鉴定的身份。最后，对血清样本进行重新分析，以定量选定的代谢物以及先前选择作为HCC候选生物标志物的其他代谢物。采用选择性反应监测（SRM）在耦合UPLC的三重四极线性离子阱（QqQLIT）上进行同位素稀释定量。UPLC-QTOF数据的统计分析确定了274个单同位素离子质量，HCC病例和肝硬化对照组的离子强度有统计学意义差异。通过对数据库的质量检索，获得了158个离子的推定鉴定。我们验证了选定的推定鉴定物的身份，包括甘胆酸（GCA）、糖脱氧胆酸（GDCA）、3 β、6 β -二羟基-5 β -胆碱-24-酸、油酰肉碱和Phe-Phe。基于srm的定量证实HCC和肝硬化对照组在胆汁酸代谢物、长链肉碱和小肽的代谢物水平上存在显著差异。我们的研究为使用基于LC-MS/MS的代谢组学发现血清生物标志物的适当实验设计和计算方法提供了有用的见解。该研究确定了候选生物标志物，HCC病例和肝硬化对照之间代谢物水平有显著变化。这是第一个基于ms的代谢生物标志物发现研究，该研究在埃及受试者中发现了区分早期HCC和肝硬化患者的候选代谢物。
Although hepatocellular carcinoma (HCC) has been subjected to continuous investigation and its symptoms are well known, early-stage diagnosis of this disease remains difficult and the survival rate after diagnosis is typically very low (3–5%). Early and accurate detection of metabolic changes in the sera of patients with liver cirrhosis can help improve the prognosis of HCC and lead to a better understanding of its mechanism at the molecular level, thus providing patients with in-time treatment of the disease. In this study, we compared metabolite levels in sera of 40 HCC patients and 49 cirrhosis patients from Egypt by using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS). Following data preprocessing, the most relevant ions in distinguishing HCC cases from cirrhotic controls are selected by statistical methods. Putative metabolite identifications for these ions are obtained through mass-based database search. The identities of some of the putative identifications are verified by comparing their MS/MS fragmentation patterns and retention times with those from authentic compounds. Finally, the serum samples are reanalyzed for quantitation of selected metabolites along with other metabolites previously selected as candidate biomarkers of HCC. This quantitation was performed using isotope dilution by selected reaction monitoring (SRM) on a triple quadrupole linear ion trap (QqQLIT) coupled to UPLC. Statistical analysis of the UPLC-QTOF data identified 274 monoisotopic ion masses with statistically significant differences in ion intensities between HCC cases and cirrhotic controls. Putative identifications were obtained for 158 ions by mass based search against databases. We verified the identities of selected putative identifications including glycholic acid (GCA), glycodeoxycholic acid (GDCA), 3beta, 6beta-dihydroxy-5beta-cholan-24-oic acid, oleoyl carnitine, and Phe-Phe. SRM-based quantitation confirmed significant differences between HCC and cirrhotic controls in metabolite levels of bile acid metabolites, long chain carnitines and small peptide. Our study provides useful insight into appropriate experimental design and computational methods for serum biomarker discovery using LC-MS/MS based metabolomics. This study has led to the identification of candidate biomarkers with significant changes in metabolite levels between HCC cases and cirrhotic controls. This is the first MS-based metabolic biomarker discovery study on Egyptian subjects that led to the identification of candidate metabolites that discriminate early stage HCC from patients with liver cirrhosis.
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HMDB：人类代谢组数据库。
影响因子：
14.9
作者：
Wishart, David S;Tzur, Dan;Knox, Craig;Eisner, Roman;Guo, An Chi;Young, Nelson;Cheng, Dean;Jewell, Kevin;Arndt, David;Sawhney, Summit;Fung, Chris;Nikolai, Lisa;Lewis, Mike;Coutouly, Marie-Aude;Forsythe, Ian;Tang, Peter;Shrivastava, Savita;Jeroncic, Kevin;Stothard, Paul;Amegbey, Godwin;Block, David;Hau, David D;Wagner, James;Miniaci, Jessica;Clements, Melisa;Gebremedhin, Mulu;Guo, Natalie;Zhang, Ying;Duggan, Gavin E;Macinnis, Glen D;Weljie, Alim M;Dowlatabadi, Reza;Bamforth, Fiona;Clive, Derrick;Greiner, Russ;Li, Liang;Marrie, Tom;Sykes, Brian D;Vogel, Hans J;Querengesser, Lori
通讯作者：
Querengesser, Lori
DOI：
10.1111/1467-9868.00346
发表时间：
2002-01-01
影响因子：
5.8
作者：
Storey, JD
通讯作者：
Storey, JD
影响因子：
1.8
作者：
Nicholson, JK;Lindon, JC;Holmes, E
通讯作者：
Holmes, E
影响因子：
64.8
作者：
Watanabe, M;Houten, SM;Auwerx, J
通讯作者：
Auwerx, J
影响因子：
2.5
作者：
Smith, CA;O'Maille, G;Siuzdak, G
通讯作者：
Siuzdak, G