Abstract：
BACKGROUND: Hepatocellular cancer (HCC) is one of the most harmful tumors to human health. Currently, there is still a lack of highly sensitive and specific HCC biomarkers in clinical practice. In this study, we aimed to explore the diagnostic performance of prostaglandin A2 (PGA2) for the early detection of HCC.
METHODS: Untargeted metabolomic analyses on normal control (NC) and HCC participants in the discovery cohort were performed, and PGA2 was identified to be dysregulated in HCC. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detecting serum PGA2 was established and applied to validate the dysregulation of PGA2 in another independent validation cohort. Receiver operating characteristic (ROC), decision curve analysis (DCA) and some other statistical analyses were performed to evaluate the diagnostic performance of PGA2 for HCC.
RESULTS: At first, PGA2 was found to be dysregulated in HCC in untargeted metabolomic analyses. Then a precise quantitative LC-MS/MS method for PGA2 has been established and has passed rigorous method validation. Targeted PGA2 analyses confirmed that serum PGA2 was decreased in HCC compared to normal-risk NC and high-risk cirrhosis group. Subsequently, PGA2 was identified as a novel biomarker for the diagnosis of HCC, with an area under the ROC curve (AUC) of 0.911 for differentiating HCC from the combined NC + cirrhosis groups. In addition, PGA2 exhibited high performance for differentiating small-size (AUC = 0.924), early-stage (AUC = 0.917) and AFP (-) HCC (AUC = 0.909) from the control groups. The combination of PGA2 and AFP might be useful in the surveillance of risk population for HCC and early diagnosis of HCC.
CONCLUSIONS: This study establishes that PGA2 might be a novel diagnostic biomarker for HCC.
METHODS: Untargeted metabolomic analyses on normal control (NC) and HCC participants in the discovery cohort were performed, and PGA2 was identified to be dysregulated in HCC. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for detecting serum PGA2 was established and applied to validate the dysregulation of PGA2 in another independent validation cohort. Receiver operating characteristic (ROC), decision curve analysis (DCA) and some other statistical analyses were performed to evaluate the diagnostic performance of PGA2 for HCC.
RESULTS: At first, PGA2 was found to be dysregulated in HCC in untargeted metabolomic analyses. Then a precise quantitative LC-MS/MS method for PGA2 has been established and has passed rigorous method validation. Targeted PGA2 analyses confirmed that serum PGA2 was decreased in HCC compared to normal-risk NC and high-risk cirrhosis group. Subsequently, PGA2 was identified as a novel biomarker for the diagnosis of HCC, with an area under the ROC curve (AUC) of 0.911 for differentiating HCC from the combined NC + cirrhosis groups. In addition, PGA2 exhibited high performance for differentiating small-size (AUC = 0.924), early-stage (AUC = 0.917) and AFP (-) HCC (AUC = 0.909) from the control groups. The combination of PGA2 and AFP might be useful in the surveillance of risk population for HCC and early diagnosis of HCC.
CONCLUSIONS: This study establishes that PGA2 might be a novel diagnostic biomarker for HCC.
摘要：
背景：肝细胞癌（HCC）是对人类健康最有害的肿瘤之一。目前,在临床实践中仍然缺乏高度敏感和特异性的HCC生物标志物。在这项研究中,我们旨在探讨前列腺素A2(PGA2)对肝癌早期诊断的价值.
方法：对发现队列中的正常对照（NC）和HCC参与者进行非靶向代谢组学分析，PGA2在HCC中被鉴定为失调。建立了检测血清PGA2的液相色谱-串联质谱（LC-MS/MS）方法，并将其用于验证另一个独立验证队列中PGA2的失调。接收机工作特性(ROC),进行了决策曲线分析(DCA)和其他一些统计分析,以评估PGA2对HCC的诊断性能.
结果：首先，在非靶向代谢组学分析中发现PGA2在HCC中失调。然后建立了PGA2的精确定量LC-MS/MS方法，并通过了严格的方法验证。靶向PGA2分析证实，与正常风险NC和高风险肝硬化组相比，HCC中的血清PGA2降低。随后，PGA2被确定为诊断HCC的新生物标志物，ROC曲线下面积（AUC）为0.911，用于区分HCC与联合NC+肝硬化组。此外,PGA2在区分小尺寸（AUC=0.924）方面表现出高性能，早期（AUC=0.917）和AFP（-）HCC（AUC=0.909）来自对照组。PGA2和AFP的组合可能有助于HCC危险人群的监测和HCC的早期诊断。
结论：本研究表明PGA2可能是一种新型的HCC诊断生物标志物。
方法：对发现队列中的正常对照（NC）和HCC参与者进行非靶向代谢组学分析，PGA2在HCC中被鉴定为失调。建立了检测血清PGA2的液相色谱-串联质谱（LC-MS/MS）方法，并将其用于验证另一个独立验证队列中PGA2的失调。接收机工作特性(ROC),进行了决策曲线分析(DCA)和其他一些统计分析,以评估PGA2对HCC的诊断性能.
结果：首先，在非靶向代谢组学分析中发现PGA2在HCC中失调。然后建立了PGA2的精确定量LC-MS/MS方法，并通过了严格的方法验证。靶向PGA2分析证实，与正常风险NC和高风险肝硬化组相比，HCC中的血清PGA2降低。随后，PGA2被确定为诊断HCC的新生物标志物，ROC曲线下面积（AUC）为0.911，用于区分HCC与联合NC+肝硬化组。此外,PGA2在区分小尺寸（AUC=0.924）方面表现出高性能，早期（AUC=0.917）和AFP（-）HCC（AUC=0.909）来自对照组。PGA2和AFP的组合可能有助于HCC危险人群的监测和HCC的早期诊断。
结论：本研究表明PGA2可能是一种新型的HCC诊断生物标志物。
