Reprogramming of lipid metabolism in hepatocellular carcinoma resulting in downregulation of phosphatidylcholines used as potential markers for diagnosis and prediction

ABSTRACT

Background

Aberrant methylation and metabolic perturbations may deepen our understanding of hepatocarcinogenesis and help identify novel biomarkers for diagnosing hepatocellular carcinoma (HCC). We aimed to develop an HCC model based on a multi-omics.

Research design and methods

Four hundred patient samples (200 with HCC and 200 with hepatitis B virus-related liver disease (HBVLD)) were subjected to liquid chromatography-mass spectrometry and multiplex bisulfite sequencing. Integrative analysis of clinical data, CpG data, and metabolome for the 20 complete imputation datasets within a for-loopwas used to identify biomarker.

Results

Totally, 1,140 metabolites were annotated, of which 125 were differentially expressed. Lipid metabolism reprogramming in HCC, resulting in phosphatidylcholines (PC) significantly downregulated, partly due to the altered mitochondrial beta-oxidation of fatty acids with diverse chain lengths. Age, sex, serum-fetoprotein levels, cg05166871,cg14171514, cg18772205, PC (O-16:0/20:3(8Z, 11Z, 14Z)), and PC (16:1(9Z)/P-18:0) were used to develop the HCC model. The model presented a good diagnostic and an acceptable predictive performance. The cumulative incidence of HCC in low- and high-risk groups of HBVLD patients were 1.19% and 21.40%, respectively (p = 0.0039).

Conclusions

PCs serve as potential plasma biomarkers and help identify patients with HBVLD at risk of HCC who should be screened for early diagnosis and intervention.

KEYWORDS:

• HCC
• lipid metabolism reprogramming
• phosphatidylcholine (PC)
• integrative analysis
• diagnosis
• prediction

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

Kang Li, Wanting Shi, Yi Song performed the data analyses and wrote the manuscript; Ling Qin, Chaoran Zang, Tingting Mei, Ang Li, Qingkun Song contributed significantly to analysis and manuscript preparation; Yonghong Zhang contributed to the conception of the study.

Ethical approval and consent

The study was approved by the Institutional Ethics Committee of the Beijing You’An Hospital. The study obtained informed consent from all participants for the study and the use of human blood samples for clinical experiments.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

Supplemental data

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2023.2254884.

Additional information

Funding

This paper was supported grants Beijing Hospitals Authority Youth Programme (code: QML20211709), Capital’s Funds of Health Improvement and Research (CFH2020-1-2182),National Key R&D Program of China (2020YFE0202400), Beijing Municipal Science & Technology Commission (Z171100001017078) and Beijing Key Laboratory (BZ0373).