Identification of novel biomarkers of hepatocellular carcinoma by high-definition mass spectrometry: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry and desorption electrospray ionization mass spectrometry imaging.

Abstract

RATIONALE:

Hepatocellular carcinoma (HCC) is a highly malignant disease for which the development of prospective or prognostic biomarkers is urgently required. Although metabolomics is widely used for biomarker discovery, there are some bottlenecks regarding the comprehensiveness of detected features, reproducibility of methods, and identification of metabolites. In addition, information on localization of metabolites in tumor tissue is needed for functional analysis. Here, we developed a wide-polarity global metabolomics (G-Met) method, identified HCC biomarkers in human liver samples by high-definition mass spectrometry (HDMS), and demonstrated localization in cryosections using desorption electrospray ionization MS imaging (DESI-MSI) analysis.

METHODS:

Metabolic profiling of tumor (n = 38) and nontumor (n = 72) regions in human livers of HCC was performed by an ultrahigh-performance liquid chromatography quadrupole time-of-flight MS (UHPLC/QTOFMS) instrument equipped with a mixed-mode column. The HCC biomarker candidates were extracted by multivariate analyses and identified by matching values of the collision cross section and their fragment ions on the mass spectra obtained by HDMS. Cryosections of HCC livers, which included both tumor and nontumor regions, were analyzed by DESI-MSI.

RESULTS:

From the multivariate analysis, m/z 904.83 and m/z 874.79 were significantly high and low, respectively, in tumor samples and were identified as triglyceride (TG) 16:0/18:1(9Z)/20:1(11Z) and TG 16:0/18:1(9Z)/18:2(9Z,12Z) using the synthetic compounds. The TGs were clearly localized in the tumor or nontumor areas of the cryosection.

CONCLUSIONS:

Novel biomarkers for HCC were identified by a comprehensive and reproducible G-Met method with HDMS using a mixed-mode column. The combination analysis of UHPLC/QTOFMS and DESI-MSI revealed that the different molecular species of TGs were associated with tumor distribution and were useful for characterizing the progression of tumor cells and discovering prospective biomarkers.

• Authors: Koshi Nagai, Baasanjav Uranbileg, Zhen Chen, Amane Fujioka, Takahiro Yamazaki, Yotaro Matsumoto, Hiroki Tsukamoto, Hitoshi Ikeda, Yutaka Yatomi, Hitoshi Chiba, Shu-Ping Hui, Toru Nakazawa, Ritsumi Saito, Seizo Koshiba, Junken Aoki, Daisuke Saigusa, Yoshihisa Tomioka
• Journal: Rapid communications in mass spectrometry : RCM (Rapid Commun Mass Spectrom) Vol. 34 Suppl 1 Pg. e8551 (Apr 2020) ISSN: 1097-0231 [Electronic] England
• PMID: 31412144 (Publication Type: Journal Article)
• Copyright: © 2019 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.

Chemical References

• Biomarkers, Tumor

Topics

• Biomarkers, Tumor (analysis, metabolism)
• Carcinoma, Hepatocellular (diagnosis, metabolism)
• Chromatography, High Pressure Liquid
• Humans
• Liver (metabolism, pathology)
• Liver Neoplasms (diagnosis, metabolism)
• Metabolome
• Spectrometry, Mass, Electrospray Ionization
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization