The Application Value of Lipoprotein Particle Numbers in the Diagnosis of HBV-Related Hepatocellular Carcinoma with BCLC Stage 0-A.

Duo Zuo,Jiawei Xiao,Haohua An,Li Ren,Jianhua Li

doi:10.3390/jpm11111143

Abstract

Early diagnosis is essential for improving the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aims to explore the clinical value of lipoprotein subfractions in the diagnosis of hepatitis B virus (HBV)-related HCC. Lipoprotein subfractions were detected by 1H-NMR spectroscopy, and the pattern-recognition method and binary logistic regression were performed to classify distinct serum profiles and construct prediction models for HCC diagnosis. Differentially expressed proteins associated with lipid metabolism were detected by LC-MS/MS, and the potential prognostic significance of the mRNA expression was evaluated by Kaplan–Meier survival analysis. The diagnostic panel constructed from the serum particle number of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL-1~LDL-6) achieved higher accuracy for the diagnosis of HBV-related HCC and HBV-related benign liver disease (LD) than that constructed from serum alpha-fetoprotein (AFP) alone in the training set (AUC: 0.850 vs. AUC: 0.831) and validation set (AUC: 0.926 vs. AUC: 0.833). Furthermore, the panel achieved good diagnostic performance in distinguishing AFP-negative HCC from AFP-negative LD (AUC: 0.773). We also found that lipoprotein lipase (LPL) transcript levels showed a significant increase in cancerous tissue and that high expression was significantly positively correlated with the poor prognosis of patients. Our research provides new insight for the development of diagnostic biomarkers for HCC, and abnormal lipid metabolism and LPL-mediated abnormal serum lipoprotein metabolism may be important factors in promoting HCC development.

Highlights

Hepatocellular carcinoma (HCC) is increasingly recognized as a serious, worldwide public health concern
We analyzed and found that the lipoprotein lipase (LPL) mRNA expression level in cancerous tissues of HCC patients showed a significant increase compared with paracancerous tissues, and the high expression of LPL showed a significant positive correlation with the poor prognosis of HCC patients from TCGA database
The results clearly indicate that the lipidomic biomarker panel constructed with the particle numbers of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL)-1, LDL-2, LDL-3, LDL-4, LDL-5, and LDL-6 could be used in the diagnosis of HCC

Summary

Introduction

Hepatocellular carcinoma (HCC) is increasingly recognized as a serious, worldwide public health concern. It is the sixth-most common malignancy and the fourth leading cause of cancer death in the world, with approximately 841,000 new cases and 782,000 deaths worldwide each year. The most common risk factors for HCC are chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV); in the vast majority of cases, HCC occurs in individuals with cirrhosis caused by chronic infection with HBV in China [1]. It has been reported that the overall median survival time of advanced-stage HCC is only 6–10 months; for early-stage HCC, surgical treatments such as radiofrequency ablation, selective hepatectomy, and liver transplantation can increase the 5-year survival rate to 60–80% [3]. Alpha-fetoprotein (AFP) is the most commonly used serological test for the early diagnosis and monitoring of the development of HCC; owing to a lack of sensitivity and specificity, the application of AFP in the diagnosis and prognosis monitoring of HCC is limited [5]

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