INTRODUCTION Diabetes and cancer are among the most frequent causes of death worldwide. Recent epidemiological findings have indicated a link between diabetes and cancer in several organs, particularly the liver. A number of epidemiological studies have demonstrated that diabetes is an established independent risk factor for hepatocellular carcinoma (HCC). However, the metabolites connecting diabetes and HCC remains less well understood. OBJECTIVES The study aimed to identify clinical and metabolomics differences of HCC from patients with/without diabetes using comprehensive global metabolomics analysis. METHODS Metabolite profiling was conducted with the Metabolon platform for 120 human diabetes/non-diabetes HCC tumor/normal tissues. Standard statistical analyses were performed using the Partek Genomics Suite on log-transformed data. Principal component analysis (PCA) was conducted using all and dysregulated metabolites. RESULTS We identified a group of metabolites that are differentially expressed in the tumor tissues of diabetes HCC compared to non-diabetes HCC patients. Meanwhile, we also identified a group of metabolites that are differentially expressed in the matched normal liver tissues of diabetes HCC compared to non-diabetes HCC patients. Some metabolites are consistently dysregulated in the tumor or matched normal tissues of HCC with or without diabetes. However, some metabolites, including 2-hydroxystearate, were only overexpressed in the tumor tissues of HCC with diabetes and associated with the glucose level. CONCLUSION Metabolic profiling identifies distinct dysregulated metabolites in HCC patients with/without diabetes.

中文翻译：

---

肝细胞癌糖尿病患者的临床和代谢组学分析。

简介糖尿病和癌症是全世界最常见的死亡原因之一。最近的流行病学研究结果表明，糖尿病与某些器官（尤其是肝脏）的癌症之间存在联系。大量流行病学研究表明，糖尿病是肝细胞癌（HCC）的既定独立危险因素。然而，关于糖尿病和肝癌的代谢物仍然知之甚少。目的本研究旨在通过全面的全局代谢组学分析来确定患有/不患有糖尿病患者的肝癌临床和代谢组学差异。方法使用Metabolon平台对120例人类糖尿病/非糖尿病HCC肿瘤/正常组织进行代谢物谱分析。使用Partek Genomics Suite对转换后的数据进行标准统计分析。使用所有和失调的代谢物进行主成分分析（PCA）。结果我们确定了一组与非糖尿病HCC患者相比在糖尿病HCC肿瘤组织中差异表达的代谢物。同时，我们还鉴定了一组与非糖尿病HCC患者相比在匹配的糖尿病HCC正常肝组织中差异表达的代谢物。在患有或不患有糖尿病的肝癌的肿瘤或匹配的正常组织中，某些代谢物始终失调。然而，某些代谢物，包括2-羟基硬脂酸酯，仅在患有糖尿病的HCC肿瘤组织中过表达，并且与葡萄糖水平有关。结论代谢谱分析在患有/不患有糖尿病的HCC患者中发现了不同的代谢产物失调。