Metabolomic Profiles for HBV Related Hepatocellular Carcinoma Including Alpha-Fetoproteins Positive and Negative Subtypes

Abstract

Background: Hepatocellular carcinoma (HCC) is very common globally prevalent cancer. Due to its poor clinical prognosis, increasing the diagnostic rate of HCC is urgently needed. Herein, we validate discovered metabolomic biomarkers to distinguish Hepatitis B virus (HBV)-related HCC, including alpha-fetoprotein (AFP) negative (AFP–) and positive (AFP+) individuals.Methods: We recruited 130 HCC subjects (independent case-control, randomized clinical cohorts) to our study. We separated the subjects randomly into two panels: (1) 58 individuals for the discovery panel; and (2) 72 individuals for the validation panel. For each panel, gender and age-matched hepatitis B group (HBG) and healthy group were included as controls. Plasma samples were collected for metabolic profiling by liquid chromatography—mass spectrometry—based metabolomics assays. We applied both non-targeted metabolomics analyses and targeted metabolomics analyses. Significantly changed metabolites (SCMs) were identified. The power of SCMs to discriminate HCC and HBG or healthy group was determined by receiver operating characteristic curve (ROC) analysis.Results: Ten SCMs were selected form the discovery panel, and further verified in the validation panel. ROC analyses indicated that 1 SCMs (LysoPC (24:0)) could discriminate HCC from HBG (AUC = 0.765). Further, 8 SCMs including (LysoPC (17:0), LysoPC (20:4(8Z,11Z,14Z,17Z)), LysoPC (22:0), LysoPC (24:0), PE (P-16:0/22:4(7Z,10Z,13Z,16Z)), SM (d18:1/22:1(13Z)), Creatinine, and L-Isoleucine) displayed a heightened ability to discriminate between HCC and healthy controls (AUC were more than 0.800). Most of these SCMs were important in lipid metabolism.Conclusions: LysoPC (24:0) could distinguished HCC from HBG, and 8 SCMs distinguished HCC from healthy controls. LysoPC and other metabolites have the potential to serve as non-invasive biomarkers for HBV related AFP– and AFP+ HCC.

The Landscape Of Alpha Fetoprotein In Hepatocellular Carcinoma: Where Are We?

“…Liu et al concluded that des-gamma-carboxyprothrombin (DCP) can distinguish AFP-negative HBV-related HCC from chronic HBV infection (AUC = 0.731) or LC (AUC = 0.685) 48 . Several studies have attempted to combine multiple biomarkers [54][55][56][57][58][59][60][61] or serological examinations [62][63][64][65][66] . With the help of proteomics technology, researchers have identified some abnormally expressed proteins that were verified in various cancers [67][68][69][70] to construct a logistic regression model, which had good performance in distinguishing AFP-negative HCC 60 .…”

New Blood Biomarkers for the Diagnosis of AFP-Negative Hepatocellular Carcinoma

“…The detection of disease-related molecules in blood is simple and non-invasive and is widely regarded as the best choice for disease screening and diagnosis. In recent years, many biomarkers in blood have been identified and evaluated for the diagnosis of ANHC ( Figure 1 ), such as genetic biomarkers, proteins, and also metabolic biomarkers ( 31 ).…”

N‐glycan fingerprint predicts alpha‐fetoprotein negative hepatocellular carcinoma: A large‐scale multicenter study

“…However, the majority of these potential candidates still have shown poor specificity and sensitivity in extending independent validation. 11,12 Des-gamma-carboxyprothrombin (DCP) was once proposed to be a better HCC diagnostic marker, investigations have reported that the area under the receiver operating characteristic (AUC) of DCP is only 0.731 for diagnosing ANHCC. 13 Some other biomarkers including glypican-3, 14 Golgi protein-73 15 and micro-RNAs 16 are promising for ANHCC monitoring.…”