Prognostic and survival impact of BCL9 and RPS6KB1 copy number variation detected from circulating free DNA in hepatocellular carcinoma

ABSTRACT

Background

Circulating cell-free DNA (cfDNA) is a noninvasive substitute to liver biopsy for hepatocellular carcinoma (HCC) molecular profiling. This study aimed to use cfDNA to investigate copy number variation (CNV) in the BCL9 and RPS6KB1 genes and its impact on prognosis in HCC.

Methods

Real-Time Polymerase Chain Reaction was used to determine the CNV and cfDNA integrity index in 100 HCC patients.

Results

CNV gain in BCL9 and RPS6KB1 genes was detected in 14% and 24% of patients, respectively. Gain in CNV of BCL9 associated with risk of HCC in alcohol drinkers and hepatitis C seropositivity. In patients with RPS6KB1 gain, HCC risk increased with a high body mass index, smoking, schistosomiasis, and Barcelona clinical liver cancer stage (BCLC) A. Gain in both genes showed a high risk of HCC with elevated liver enzymes, Schistosomiasis, BCLC C, and PS > 1. The integrity of cfDNA was higher in patients with CNV gain in RPS6KB1 than those harboring CNV gain in BCL9. Lastly, BCL9 gain and BCL9 + RPS6KB1 gain led to higher mortality rates and reduced survival times.

Conclusion

cfDNA was used to detect BCL9 and RPS6KB1 CNVs, which influence prognosis and can be used as independent predictors of HCC patient survival.

KEYWORDS:

• Hepatocarcinogenes
• copy number variation profiling
• liquid biopsy
• circulating cell-free DNA (cfDNA)
• BCL9
• RPS6KB1

Declaration of interest

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.

Reviewers disclosure

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

Authors’ contributions

S.Y. conceived the study, shared in experiments and analysis of results and shared writing and revising manuscript; R.E.E.: statistical analysis, shared writing manuscript; E.A.A.: shared in experiments, analysis of results, and shared writing manuscript; M.H.: clinical examinations, conceptualization, T.E.: shared patient data curation, writing, and revising manuscript.

Ethical approval and consent

This study was approved by the Medical Research Ethics Committee of the National Research Centre, Dokki, Cairo, Egypt. The study obtained informed consent from all participants for the study and the use of human blood samples for clinical experiments.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2023.2182191

Additional information

Funding

This paper was not funded.