Identification of serum biomarkers associated with hepatitis B virus-related hepatocellular carcinoma and liver cirrhosis using mass-spectrometry-based metabolomics

Abstract

Hepatitis B virus (HBV) infection is a major risk factor for deaths from liver cirrhosis and hepatocellular carcinoma (HCC). With a long-term goal of improving early diagnosis, we aimed to identify specific biomarkers associated with the development of HCC and liver cirrhosis in patients with HBV infection. Serum samples from 46 HBV infected patients with HCC and liver cirrhosis and 24 age-gender matched healthy subjects were profiled by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. It was found that fatty acids and long-chain acylcarnitines were significantly elevated in HBV-related HCC patients, whereas most of the carbohydrates, amino acids, short-and medium-chain acylcarnitines, and glycerophospholipids were decreased, when compared to healthy subjects. The up-regulation of fatty acids and long-chain acylcarnitines in HCC was positively correlated with liver cirrhosis state. Logistic regression analysis indicated that palmitoylcarnitine together with arginine was an effective ''combined marker'' for diagnosing HBV-related HCC with 97.3 % sensitivity and 100 % specificity. Linoleic acid plus glucose was useful for discrimination of liver cirrhosis in HCC patients with 79.2 % sensitivity and 75 % specificity. These findings demonstrate that mass-spectrometry-based metabolomics is a promising tool that could provide special insights into tumor metabolism and identify novel biomarkers for detection of HCC and liver cirrhosis from HBV infected patients.

Plasma Lipidomic Analysis to Identify Novel Biomarkers for Hepatocellular Carcinoma

“…Besides, FFA could be utilized as metabolic substrates by the tumor cells [22]. Up-regulation of FFAs in HCC patients has also been revealed in other reports [23,24], which were consistent with our findings and might be the results of energy requirement and the synthesis of cell membrane due to aggressive cell proliferation.…”

Metabolic signatures and risk of type 2 diabetes in a Chinese population: an untargeted metabolomics study using both LC-MS and GC-MS

“…Metabolic profiling Serum metabolic profiling analysis was performed as described previously [22] in the NUS Environmental Research Institute at the National University of Singapore. Briefly, LC-MS analysis was performed on an Agilent 1290 ultrahigh pressure LC system coupled to a 6540 quadrupole time-of-flight (Q-ToF) mass detector (Agilent, Santa Clara, CA, USA) equipped with an electrospray ionisation source, at both positive and negative ion modes.…”

“…1) [23], which indicated good reproducibility and stability during the whole procedure. Structural identification of metabolic candidates followed our protocol that has been described previously [22].…”

A Systematic Evaluation of Blood Serum and Plasma Pre-Analytics for Metabolomics Cohort Studies

“…It currently provides a wide range of new opportunities for the development of biomarkers of medical interest with current applications in toxicology [7], cancer [8,9,10], cardiovascular disease [11,12], prediction of treatment outcomes [13,14,15] or “pharmacometabonomics” [16,17], and more recently metabolic modelling of the patient journey in a clinical environment [18,19]. Untargeted metabolomics is typically achieved using a range of analytical technologies, such as mass spectrometry (MS) and nuclear magnetic resonance (NMR) [20,21,22], resulting in the monitoring of hundreds to thousands of molecular species potentially involved in the molecular fingerprints of diseases.…”