RNA gene expression-based liquid biopsies for diagnosing hepatocellular carcinoma

Abstract

The incidence of non-alcoholic steatohepatitis, a significant risk factor for hepatocellular carcinoma (HCC), is on the rise, highlighting the urgent need for improved diagnostic biomarkers. To date, no systematic analysis has evaluated international studies using liquid samples to assess the utilization of RNA species as biomarkers for HCC. Liquid biopsies based on RNA expression offer more specific and sensitive diagnostic biomarkers for HCC than alpha-fetoprotein (AFP). The inclusion criteria mandated English-language articles, freely available full texts, and primary research published between January 1, 2019, and May 15, 2024. Quantitative analysis was performed using the area under the receiver operating characteristic (ROC) curve values, while qualitative analysis assessed study populations, sample sizes, and levels of evidence. A total of 19 studies were ultimately included in the review. The results indicated that liquid biopsies yielded biomarkers with higher area under the ROC curve values compared to AFP. Current studies have demonstrated, although with limitations, that RNA expression techniques can yield sensitive and specific diagnostic biomarkers. Among the evaluated studies, P-element-induced wimpy testis (PIWI) transcripts exhibited the highest potential as diagnostic biomarkers. However, key limitations include heterogeneity among the studies and inadequate level one evidence. Consequently, future randomized controlled trials should focus on validating the diagnostic utility of PIWI transcripts in a more targeted and standardized manner.

Keywords

RNA sequencing / Hepatocellular carcinoma / Diagnosis / Biomarker / Liquid biopsy

Acknowledgments

The authors would like to thank the Research Literature Review Analysis Committee at the Medical University of Americas for their feedback during the preparation of this review. This article was completed as part of the requirements for Balvinder Bobbie Saarsalu to fulfill the basic sciences requirement before commencing clinical clerkships in medicine.

Funding

None.

Conflict of interest

The authors declare that they have no competing interests.

Author contributions

Conceptualization: Balvinder Bobbie Saarsalu, Ila Chauhan

Data curation: Balvinder Bobbie Saarsalu

Formal analysis: Balvinder Bobbie Saarsalu

Methodology: Balvinder Bobbie Saarsalu

Visualization: Balvinder Bobbie Saarsalu, Shizue Mito

Writing-original draft: Balvinder Bobbie Saarsalu, Ila Chauhan

Writing-review & editing: Jeevan Divakaran, Shizue Mito

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data

Data are available from the corresponding author on reasonable request.

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