Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of death worldwide. Due to latent liver disease, late diagnosis, and nonresponse to systemic treatments, surgical resection and/or biopsy specimens are still generally considered as the gold standard by clinicians for clinical decision-making until now. Since the conventional tissue biopsy is invasive and contains small tissue samples, it is unable to represent tumor heterogeneity or monitor dynamic tumor progression. Therefore, it is imperative to find a new less invasive or noninvasive diagnostic strategy to detect HCC at an early stage and to monitor HCC recurrence. Over the past years, a new diagnostic concept known as “liquid biopsy” has emerged with substantial attention. Liquid biopsy is noninvasive and allows repeated analyses to monitor tumor recurrence, metastasis or treatment responses in real time. With the advanced development of new molecular techniques, HCC circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) detection have achieved interesting and encouraging results. In this review, we focus on the clinical applications of CTCs and ctDNA as key components of liquid biopsy in HCC patients.

Novel Liquid Biopsy Test Based on a Sensitive Methylated SEPT9 Assay for Diagnosing Hepatocellular Carcinoma

“…ctDNA is one of the targets in liquid biopsies and carries information on tumor‐specific genetic or epigenetic alterations. DNA methylation is one of these epigenetic alterations, and several studies have investigated ctDNA methylation in various genes . In this study, we focused on SEPT9 methylation.…”

Using circulating tumor DNA as a novel biomarker to screen and diagnose hepatocellular carcinoma: A systematic review and meta‐analysis

“…Applying novel molecular technologies to liquid biopsies has advanced our understanding of the effect of ctDNA detection on HCC diagnosis. 1,12 In this diagnostic metaanalysis, we aimed to incorporate these published results for the first time and systematically estimate the diagnostic accuracy of ctDNA for HCC. In our meta-analysis, compared with the group of quantitative analysis, the group of qualitative analysis yielded a lower SEN (0.568 vs 0.722) and AUC (0.787 vs 0.880), and that was probably because some genetic loci selected for test were predominantly expressed in non-HCC individuals.…”

“…Liver cancer, with over 841 000 patients globally, has currently become the second most frequent reason for tumor-related deaths. 1,2 Hepatocellular carcinoma (HCC), as the most common pathologic subtype of primary liver tumors, occupies approximately 90% of all patients. 2,3 The prognosis of untreated HCC patients is undesirable with a median survival of 2-14 months.…”

<p>Impact of Next-Generation Sequencing on Outcomes in Hepatocellular Carcinoma: How Precise Are We Really?</p>

“…These results demonstrate that using existing enrichment and detection technologies, sensitivity for CTC remains poor. 34 However, a recent subset study from the SORAMIC trial (Y 90 +sorafenib vs Y 90 alone), applied NGS to cfDNA to predict therapy response by detecting changes in mutational variants and frequency over time in patients with advanced HCC undergoing therapy. 35 While this application was only on a small subset of patients, it demonstrates the significant potential for gaining a wealth of information from an easily obtained sample.…”