Metabolic Profiling Identified a Novel Biomarker Panel for Metabolic Syndrome-Positive Hepatocellular Cancer.

Lin-Lin Cao,Lin Pei,Hui Wang,Jingwen Cui,Mei Jia,Zhihong Yue,Li Qin,Yuanxiao Wang,Yi Han,Boyu Liu

doi:10.3389/fendo.2021.816748

Abstract

Metabolic syndrome (MetS) is an independent risk factor for hepatocellular cancer (HCC). Currently, there is no highly sensitive and specific biomarkers for HCC surveillance in MetS population. Metabolomics has been reported as a powerful technology for biomarker discovery. In the present study, we aimed to explore novel biomarkers with high sensitivity and specificity for MetS-positive [MetS(+)] HCC by metabolomic analysis. At first, many serum metabolites were found dysregulated in MetS(+) HCC individuals. Validation of the dysregulated metabolites by targeted metabolite analyses revealed that serum L-glutamic acid (L-glu), pipecolic acid (PA) and 7-methylguanine (7-mG) were increased in MetS(+) HCC compared to MetS group. Then a biomarker panel including L-glu, PA and alpha-fetoprotein (AFP) was identified as a novel biomarker for the diagnosis of MetS(+) HCC. Receiver operating characteristic (ROC) curve was drawn and the area under the ROC curve (AUC) was 0.87 for discriminating MetS(+) HCC from MetS group. The biomarker panel was capable of detecting small (AUC = 0.82) and early-stage (AUC = 0.78) tumors as well. Moreover, it exhibited great diagnostic performance (AUC = 0.93) for discriminating MetS(+) HCC from other MetS-associated cancers, including colorectal cancer and gastric cancer. Collectively, our study establishes a novel diagnostic tool for MetS(+) HCC.

Highlights

Hepatocellular cancer (HCC) is the most common primary liver cancer and represents a seriously threat to human health
Metabolic profiling of serum samples from patients with Metabolic syndrome (MetS) and MetS(+) hepatocellular cancer (HCC) in the discovery cohort was performed, and pooled QC samples were inserted into batches to evaluate the stability of the analytical method
We found that L-glutamic acid (L-glu) and 7-mG were upregulated significantly in MetS compared to healthy controls (HC) individuals, while pipecolic acid (PA) showed no significant difference between MetS and HC group, indicating that the levels of L-glu and 7-mG, but not PA, were further affected as a consequence of the MetS in HCC patients

Summary

Introduction

Hepatocellular cancer (HCC) is the most common primary liver cancer and represents a seriously threat to human health. Considerable progress has been achieved in the diagnosis and treatment of HCC during the past few decades, the prognosis of HCC is still very poor, possibly due to the lack of obvious symptoms in the early stages and the delay in diagnosis of the disease [2]. It has been reported that tumors diagnosed at early stages are suitable for curative therapy, with a median overall survival (OS) of exceeding 60 months, whereas the median OS of patients with advancedstage HCC is only 11 months [3]. Early detection of HCC in high-risk populations is essential to improve the prognosis of HCC patients.

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