Abstract Hepatocellular carcinoma (HCC) is a typical cancer that has region specified analysis with the incidence of hepatitis C virus (HCV) infection. This study was conducted to improve the understanding of metabolic alterations associated with HCV induced HCC which can open up new strategies to monitor the high risk of HCC. Samples of the subjects with HCV, HCV induced chronic liver disease (CLD), HCV induced HCC, and healthy controls (HS) were collected after complete blood count (CBC), hepatitis viral load, α-fetoprotein (AFP), liver function tests, and albumin. A total of 147 serum samples including HCC (n=11), CLD (n=24), HCV (n=71), and HS (n=41) were analyzed by LC-ESI-MS/MS. The 21 compounds were found to be responsible for group discrimination after the application of chemometric tools. N-fructosyl tyrosine and hydroxyindoleacetic acid showed an increase in level whereas L-aspartyl-L-phenylalanine and thyroxine showed a consistent decrease in the progression of HCV to HCC in comparison with HS indicating their importance for early detection. The biological pathways such as glycerophospholipid metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism and tryptophan metabolism showed alteration in some metabolites. The method was internally validated by ROC plot showing AUC value for HS, HCV, CLD, and HCC as 0.99, 1, 1, and 0.89, respectively; while 16 blind samples were also validated with 93% specificity. The untargeted metabolomics investigation of HCV, CLD, and HCC can help to understand the progression of HCV-induced HCC. It reveals significant differences in metabolites to predict prognostic and diagnostic markers.

中文翻译：

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使用 LC-ESI-MS/MS 了解丙型肝炎病毒诱导的肝细胞癌的代谢组学方法

摘要 肝细胞癌（HCC）是一种典型的癌症，与丙型肝炎病毒（HCV）感染的发病率有区域特异性分析。进行这项研究是为了提高对与 HCV 诱导的 HCC 相关的代谢改变的理解，这可以开辟新的策略来监测 HCC 的高风险。在全血细胞计数（CBC）、肝炎病毒载量、甲胎蛋白（AFP）、肝功能检查后收集HCV、HCV诱导的慢性肝病（CLD）、HCV诱导的HCC和健康对照（HS）的样本，和白蛋白。通过 LC-ESI-MS/MS 分析了总共 147 个血清样品，包括 HCC (n=11)、CLD (n=24)、HCV (n=71) 和 HS (n=41)。在应用化学计量学工具后，发现这 21 种化合物是造成群体歧视的原因。N-果糖基酪氨酸和羟基吲哚乙酸显示出水平增加，而 L-天冬氨酰-L-苯丙氨酸和甲状腺素与 HS 相比，在 HCV 向 HCC 的进展方面显示出持续下降，表明它们对早期检测的重要性。甘油磷脂代谢、苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代谢和色氨酸代谢等生物途径在某些代谢产物中显示出改变。该方法通过 ROC 图进行了内部验证，显示 HS、HCV、CLD 和 HCC 的 AUC 值分别为 0.99、1、1 和 0.89；而 16 个盲样也以 93% 的特异性进行了验证。HCV、CLD 和 HCC 的非靶向代谢组学研究有助于了解 HCV 诱导的 HCC 的进展。