Metabolomic Profiles for HBV Related Hepatocellular Carcinoma Including Alpha-Fetoproteins Positive and Negative Subtypes
Metabolomic Profiles for HBV Related Hepatocellular Carcinoma Including Alpha-Fetoproteins Positive and Negative Subtypes
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DOI：
10.3389/fonc.2019.01069
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发表时间：
2019-10-15
影响因子：
4.7
通讯作者：
Zhang, Yonghong
中科院分区：
文献类型：
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作者：
Sun, Jianping;Zhao, Yanan;Zhang, Yonghong
背景：肝细胞癌（HCC）是一种非常常见的全球性癌症。由于其临床预后差，迫切需要提高肝癌的诊断率。在此，我们验证发现的代谢组学生物标志物来区分肝炎B病毒（HBV）相关的HCC，包括甲胎蛋白（AFP）阴性（AFP-）和阳性（AFP+）individuals.Methods：我们招募了130名HCC受试者（独立病例对照，随机临床队列）到我们的研究。我们将受试者随机分为两组：（1）58人为发现组;（2）72人为验证组。对于每组，包括性别和年龄匹配的乙型肝炎B组（HBG）和健康组作为对照。通过基于液相色谱-质谱法的代谢组学分析，采集血浆样本进行代谢分析。我们应用了非靶向代谢组学分析和靶向代谢组学分析。鉴别出显著变化的代谢物（SCM）。采用受试者工作特征曲线（ROC）分析方法，确定SCMs对HCC和HBG或健康人群的区分能力。ROC曲线分析表明，1种SCMs（LysoPC（24：0））能区分HCC和HBG（AUC = 0.765）。此外，8种SCM包括（LysoPC（17：0）、LysoPC（20：4（8 Z，11 Z，14 Z，17 Z））、LysoPC（22：0）、LysoPC（24：0）、PE（P-16：0/22：4（7Z，10 Z，13 Z，16 Z））、SM（d18：1/22：1（13 Z））、肌酸和L-异亮氨酸）显示出区分HCC和健康对照的增强能力（AUC大于0.800）。结论：LysoPC（24：0）可区分HCC和HBG，8种SCM可区分HCC和健康对照。LysoPC和其他代谢产物有可能作为HBV相关AFP-和AFP+ HCC的非侵入性生物标志物。
Background: Hepatocellular carcinoma (HCC) is very common globally prevalent cancer. Due to its poor clinical prognosis, increasing the diagnostic rate of HCC is urgently needed. Herein, we validate discovered metabolomic biomarkers to distinguish Hepatitis B virus (HBV)-related HCC, including alpha-fetoprotein (AFP) negative ( AFP-) and positive (AFP+) individuals.Methods: We recruited 130 HCC subjects (independent case-control, randomized clinical cohorts) to our study. We separated the subjects randomly into two panels: ( 1) 58 individuals for the discovery panel; and (2) 72 individuals for the validation panel. For each panel, gender and age-matched hepatitis B group (HBG) and healthy group were included as controls. Plasma samples were collected for metabolic profiling by liquid chromatography-mass spectrometry-based metabolomics assays. We applied both non-targeted metabolomics analyses and targeted metabolomics analyses. Significantly changed metabolites (SCMs) were identified. The power of SCMs to discriminate HCC and HBG or healthy group was determined by receiver operating characteristic curve (ROC) analysis.Results: Ten SCMs were selected form the discovery panel, and further verified in the validation panel. ROC analyses indicated that 1 SCMs (LysoPC (24:0)) could discriminate HCC from HBG (AUC = 0.765). Further, 8 SCMs including (LysoPC (17:0), LysoPC (20:4(8Z,11Z,14Z,17Z)), LysoPC (22:0), LysoPC (24:0), PE (P-16:0/22:4(7Z,10Z,13Z,16Z)), SM (d18:1/22:1(13Z)), Creatinine, and L-Isoleucine) displayed a heightened ability to discriminate between HCC and healthy controls (AUC were more than 0.800). Most of these SCMs were important in lipid metabolism.Conclusions: LysoPC (24:0) could distinguished HCC from HBG, and 8 SCMs distinguished HCC from healthy controls. LysoPC and other metabolites have the potential to serve as non-invasive biomarkers for HBV related AFP- and AFP+ HCC.