背景:肝细胞癌(HCC)与高死亡率相关,和早期诊断导致更好的生存。肝硬化患者,特别是由于非酒精性脂肪性肝病和病毒性肝炎,发展为HCC的风险较高,并形成主要筛查组。目前肝癌的筛查方法(6个月筛查血清甲胎蛋白和超声肝脏)敏感性较低;因此,需要更好的HCC标志物筛查.
目的:我们的研究,趋势,旨在验证新的筛选标记(甲基化的Septin9,尿中挥发性有机化合物,和尿肽)用于HCC诊断,并研究这些非侵入性生物标志物在肝病中的应用。
方法:这是一个多中心,巢式病例对照研究,其中涉及比较确诊的HCC病例和肝硬化患者(对照组)之间甲基化的septin9的血浆水平。它还包括用于检测HCC特异性挥发性有机化合物和肽的尿液样品的比较。根据考文垂和沃里克郡大学医院进行的一项试点研究的结果,我们估计我们的样本量为308(n=88,29%的HCC患者;n=220,71%的肝硬化患者)。将从所有参与者收集尿液和血浆样本,并将其冷冻在-80°C,直到招募结束。气相色谱-质谱法将用于尿液中挥发性有机化合物的检测,和毛细管电泳-质谱法将用于尿肽鉴定。实时聚合酶链反应将用于血浆甲基化septin9的定性检测。该研究将由考文垂和沃里克郡大学医院的研发部门进行监测。
结果:招募阶段于2023年3月完成。TENDENCY研究目前处于分析阶段,预计将于2023年11月完成。
结论:尽管死亡率较高,但缺乏有效的肝细胞癌筛查试验。在临床实践中应用更敏感的血浆和尿液生物标志物进行肝细胞癌筛查将使我们能够在早期阶段检测到该疾病,因此,总的来说,改善HCC结果。
■DERR1-10.2196/44264。
BACKGROUND: Hepatocellular cancer (HCC) is associated with high mortality, and early diagnosis leads to better survival. Patients with cirrhosis, especially due to nonalcoholic fatty liver disease and viral hepatitis, are at higher risk of developing HCC and form the main screening group. The current screening methods for HCC (6-monthly screening with serum alpha fetoprotein and ultrasound liver) have low sensitivity; hence, there is a need for better screening markers for HCC.
OBJECTIVE: Our study, TENDENCY, aims to validate the novel screening markers (methylated septin 9, urinary volatile organic compounds, and urinary peptides) for HCC diagnosis and study these noninvasive biomarkers in liver disease.
METHODS: This is a multicenter, nested
case-control study, which involves comparing the plasma levels of methylated septin 9 between confirmed HCC cases and patients with cirrhosis (control group). It also includes the comparison of urine samples for the detection of HCC-specific volatile organic compounds and peptides. Based on the findings of a pilot study carried out at University Hospital Coventry & Warwickshire, we estimated our sample size to be 308 (n=88, 29% patients with HCC; n=220, 71% patients with cirrhosis). Urine and plasma samples will be collected from all participants and will be frozen at -80 °C until the end of recruitment. Gas chromatography-mass spectrometry will be used for urinary volatile organic compounds detection, and capillary electrophoresis-mass spectrometry will be used for urinary peptide identification. Real-time polymerase chain reaction will be used for the qualitative detection of plasma methylated septin 9. The study will be monitored by the Research and Development department at University Hospital Coventry & Warwickshire.
RESULTS: The recruitment stage was completed in March 2023. The TENDENCY study is currently in the analysis stage, which is expected to finish by November 2023.
CONCLUSIONS: There is lack of effective screening tests for hepatocellular cancer despite higher mortality rates. The application of more sensitive plasma and urinary biomarkers for hepatocellular cancer screening in clinical practice will allow us to detect the disease at earlier stages and hence, overall, improve HCC outcomes.
UNASSIGNED: DERR1-10.2196/44264.