The value of liquid biopsy in the diagnosis and staging of hepatocellular carcinoma: a systematic review

Abstract

Background: Blood-borne tumour markers in the form of circulating tumour cells (CTCs) are of intense research interest in the diagnostic and prognostic work-up of hepatocellular carcinoma (HCC).Methods: This is a meta-analysis. Using a PICO strategy, adults with HCC was the population, with the individual CTCs as the intervention and comparators. The primary outcome was the sensitivity and specificity of HCC detection with tumour specific single gene methylation alteration. Secondary outcomes were the comparison using specific assay methods and the effect of early vs. late stages on CTC positivity.We included patients with HCC who had samples taken from peripheral blood and had sufficient data to assess the outcome data. ASSIA, Cochrane library, EMbase, Medline, PubMed and the knowledge network Scotland were systematically searched with appropriate Mesh terms employed. The quality assessment of diagnostic accuracy studies (QUADAS) was used to ensure quality of data. Statistical analysis was performed using the 'Rev Man' meta-analysis soft ward for Windows. Results:The review included 36 studies, with a total of 5,853 patients. Here, we found that AFP has the highest overall diagnostic performance. The average Youden index amongst all CTC was 0.46 with a mode and median of 0.5 with highest of 0.87 and lowest of 0.01 Conclusions:The available literature provides weak evidence that there is potential in the use of CTC, however the lack of a standardised procedure in the study of CTC contribute to the lack of consensus of use.Future research should include large scaled, standardized studies for the diagnostic accuracy of CTCs.

Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population

“…Several studies have demonstrated the feasibility of liquid biopsy to detect mutations and methylation in HCC screening by next-generation sequencing (NGS) [ 21 – 25 ]. Many more studies demonstrated the applicability of single markers or their combination in HCC screening by quantitative polymerase chain reaction (qPCR) and immunoassays [ 26 – 28 ]. The most representative studies investigated the combination of methylated SEPT9 (mSEPT9) and AFP, which showed significantly higher sensitivity than any single marker alone [ 26 – 28 ].…”

“…Many more studies demonstrated the applicability of single markers or their combination in HCC screening by quantitative polymerase chain reaction (qPCR) and immunoassays [ 26 – 28 ]. The most representative studies investigated the combination of methylated SEPT9 (mSEPT9) and AFP, which showed significantly higher sensitivity than any single marker alone [ 26 – 28 ]. However, these studies were mostly case-control, and did not reflect the performance of combined markers in screening scenario.…”

Liquid biopsies to occult brain metastasis

“…However, the mutant gene responsible for the resistance was present in the circulating tumor DNA (ctDNA) isolated from the peripheral blood samples [ 7 ]. Therefore, it looks plausible to infer tumor biomarkers in the systemic circulation and other liquid biopsies that refer to circulating biomarkers in the form of DNA, RNA, proteins, and metabolites derived from tumors that can give a glimpse into cancer features [ 8 – 10 ]. If the diagnosis of neoplastic growth can be made upfront, the chance of mortality can go down; indeed, disease-free survival is possible in some cancer types, if not all [ 11 ].…”