Novel biomarkers for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis are urgently needed. We previously identified osteopontin (OPN) as a promising biomarker for the early detection of HCC. This study is to further validate the performance of OPN and identify fatty acids (FA) that could improve OPN's performance in HCC risk assessment in patients with cirrhosis. To that end, we selected 103 patients with cirrhosis under surveillance. Among them, 40 patients developed HCC during follow-up. We investigated in these 103 patients, the association between HCC incidence and prediagnostic serum levels of AFP, OPN, and 46 FAs. OPN performance was higher than AFP in detecting prediagnosis HCCs and the combination with AFP further improved OPN's performance. For patients with a diagnosis of HCC within 18 months of follow-up (HCC < 18 months), AUC for OPN + AFP was 0.77. Abundance of 11 FAs [four long-chain saturated FAs (SFA), four n-3 poly-unsaturated FAs (PUFA), and three n-6 PUFAs] were statistically different between patients who developed HCC and those who did not. Abundance changes correlated with time to diagnosis for the PUFAs, but not for the SFAs. Adding arachidic acid (20:0) and n-3 docosapentaenoic acid (22:5n3) to OPN and AFP improved the discriminatory performance (AUC = 0.83). AUC for this panel reached 0.87 for HCC < 18 months (82% sensitivity at 81% specificity). In conclusion, we identified a panel of 4 markers with strong performances that could have significant utility in HCC early detection in patients with cirrhosis under surveillance. Prevention Relevance: This study identified a panel of 4 biomarkers that identifies with high performance patients with cirrhosis at high risk for HCC. This panel could have utility in HCC early detection in patients with cirrhosis under surveillance.

中文翻译：

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一种用于肝硬化患者早期检测和风险评估肝细胞癌的新型生物标志物组

迫切需要用于肝硬化患者肝细胞癌 (HCC) 监测的新型生物标志物。我们之前将骨桥蛋白 (OPN) 确定为早期检测 HCC 的有希望的生物标志物。本研究旨在进一步验证 OPN 的性能并确定可以提高 OPN 在肝硬化患者 HCC 风险评估中的性能的脂肪酸 (FA)。为此，我们选择了 103 名接受监测的肝硬化患者。其中，40 例患者在随访期间发展为 HCC。我们在这 103 名患者中调查了 HCC 发病率与诊断前血清 AFP、OPN 和 46 种 FA 水平之间的关系。OPN 在检测诊断前 HCC 方面的性能高于 AFP，并且与 AFP 的组合进一步提高了 OPN 的性能。对于在随访 18 个月内诊断为 HCC 的患者（HCC < 18 个月），OPN + AFP 的 AUC 为 0.77。11 种 FAs [四种长链饱和 FAs (SFA)、四种 n-3 多不饱和 FAs (PUFA) 和三种 n-6 PUFAs] 的丰度在发生 HCC 的患者和未发生的患者之间存在统计学差异。丰度变化与 PUFA 的诊断时间相关，但与 SFA 无关。在 OPN 和 AFP 中添加花生酸 (20:0) 和 n-3 二十二碳五烯酸 (22:5n3) 提高了判别性能 (AUC = 0.83)。对于小于 18 个月的 HCC，该组的 AUC 达到 0.87（敏感性为 82%，特异性为 81%）。总之，我们确定了一组具有强大性能的 4 个标志物，这些标志物可能在监测肝硬化患者的 HCC 早期检测中具有重要用途。预防相关：该研究确定了一组 4 种生物标志物，这些生物标志物可识别出具有 HCC 高风险的高性能肝硬化患者。该小组可用于监测肝硬化患者的 HCC 早期检测。