Sun Jianping, Zhao Yanan, Qin Ling, Li Kang, Zhao Yan, Sun Huanqin, Zhang Ting, Zhang Yonghong
Beijing You'an Hospital, Capital Medical University, Beijing, China.
NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Front Oncol. 2019 Oct 15;9:1069. doi: 10.3389/fonc.2019.01069. eCollection 2019.
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. 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. 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. 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.
肝细胞癌（HCC）是全球非常常见的一种癌症。由于其临床预后较差，迫切需要提高HCC的诊断率。在此，我们对发现的代谢组学生物标志物进行验证，以区分乙型肝炎病毒（HBV）相关的HCC，包括甲胎蛋白（AFP）阴性（AFP-）和阳性（AFP+）个体。我们招募了130名HCC受试者（独立病例对照、随机临床队列）参与本研究。我们将受试者随机分为两个组：（1）58名个体作为发现组；（2）72名个体作为验证组。对于每个组，纳入性别和年龄匹配的乙型肝炎组（HBG）和健康组作为对照。通过基于液相色谱-质谱的代谢组学分析收集血浆样本进行代谢谱分析。我们同时应用了非靶向代谢组学分析和靶向代谢组学分析。识别出显著变化的代谢物（SCMs）。通过受试者工作特征曲线（ROC）分析确定SCMs区分HCC与HBG或健康组的能力。从发现组中选出10种SCMs，并在验证组中进一步验证。ROC分析表明，1种SCMs（溶血磷脂酰胆碱（24:0））可区分HCC与HBG（曲线下面积（AUC）=0.765）。此外，包括（溶血磷脂酰胆碱（17:0）、溶血磷脂酰胆碱（20:4(8Z,11Z,14Z,17Z)）、溶血磷脂酰胆碱（22:0）、溶血磷脂酰胆碱（24:0）、磷脂酰乙醇胺（P-16:0/22:4(7Z,10Z,13Z,16Z)）、神经酰胺（d18:1/22:1(13Z)）、肌酐和L-异亮氨酸）在内的8种SCMs显示出区分HCC与健康对照的能力增强（AUC均大于0.800）。这些SCMs大多在脂质代谢中起重要作用。溶血磷脂酰胆碱（24:0）可区分HCC与HBG，8种SCMs可区分HCC与健康对照。溶血磷脂酰胆碱和其他代谢物有潜力作为HBV相关AFP-和AFP+HCC的非侵入性生物标志物。
