Liquid Chromatography–Mass Spectrometry-Based Nontargeted Metabolomics Predicts Prognosis of Hepatocellular Carcinoma after Curative Resection

Abstract

Assessment and prediction of prognostic risk in patients with hepatocellular carcinoma (HCC) would greatly benefit the optimal treatment selection. Here, we aimed to identify the critical metabolites associated with the outcomes and develop a risk score to assess the prognosis of HCC patients after curative resection. A total of 78 serum samples of HCC patients were analyzed by liquid chromatography–mass spectrometry to characterize the metabolic profiling. A novel network-based feature selection method (NFSM) was developed to define the critical metabolites with the most discriminant capacity to outcomes. The metabolites defined by NFSM was further reduced by Cox regression analysis to generate a prognostic metabolite panelphenylalanine and choline. Furthermore, univariate and multivariate Cox regression analyses were applied to combine the metabolite panel with the presence of satellite nodes to generate a global prognostic index (GPI) score for overall survival assessment. Compared with the current clinical classification systems, including the Barcelona-clinic liver cancer stage, tumor–node–metastasis stage, and albumin–bilirubin grade, the GPI score presented comparable performance, according to the time-dependent receiver operating characteristic curves and was validated in an independent cohort, which suggested that metabolomics could serve as a helpful tool to stratify the HCC prognostic risk after operation.

Navigating through the Lipid Metabolism Maze: Diagnosis and Prognosis Metabolites of Hepatocellular Carcinoma versus Compensated Cirrhosis

“…In 2020, Wang Q et al reported a global prognostic index (GPI) score for operated HCC patients that combines a metabolite panel with satellite nodes for assessing overall survival. Compared with the current clinical classification systems, including the Barcelona clinic liver cancer (BCLC) stage, the tumor node metastasis (TNM) stage, and the albumin-bilirubin (ALBI) grade, the GPI score presented a notable performance according to the time-dependent receiver operating, and might stand as a helpful tool to stratify the HCC prognostic risk after surgery [ 34 ]. Other scientists used gas chromatography-mass spectrometry (GC-MS)-based metabolomics, identifying phenylalanine and galactose and including them in two mathematical models to predict the risk of mortality, recurrence, and metastasis with essential results.…”

Biomarkers for hepatocellular carcinoma based on body fluids and feces

“…Furthermore, an effective nomogram based on preoperative plasma metabolomics profiling was able to predict the risk of HCC recurrence after liver transplantation, thus optimizing candidate selection for transplantation[ 24 ]. Another study on a scoring system, which included phenylalanine and choline, could be used as an adjuvant tool to stratify patients who could benefit most from curative resection[ 25 ].…”

Prognosis prediction of hepatocellular carcinoma after surgical resection based on serum metabolic profiling from gas chromatography-mass spectrometry

“…In our previous study in 2014 [14], phenylalanine and 4 other metabolites (ethanolamine, acotinic acid, lactic acid, and ribose) were defined from the urinary metabolic profiling favorably to predict early recurrence of HCC. And recently [18] a prognostic metabolite panel (phenylalanine and choline) was generated for overall survival assessment from serum metabolic profiling of HCC patients by using liquid chromatography-mass spectrometry. Combined with present results, it is suggested that phenylalanine is indeed associated with the prognosis of HCC and could be used in the future prognosis evaluation.…”