Liquid Biopsy of Hepatocellular Carcinoma: Circulating Tumor-Derived Biomarkers

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide due to latent liver disease, late diagnosis, and nonresponse to systemic treatments. Till now, surgical and/or biopsy specimens are still generally used as a gold standard by the clinicians for clinical decision-making. However, apart from their invasive characteristics, tumor biopsy only mirrors a single spot of the tumor, failing to reflect current cancer dynamics and progression. Therefore, it is imperative to develop new diagnostic strategies with significant effectiveness and reliability to monitor high-risk populations and detect HCC at an early stage. In the past decade, the potent utilities of “liquid biopsy” have attracted intense concern and were developed to evaluate cancer progression in several clinical trials. “Liquid biopsies” represent a series of noninvasive tests that detect cancer byproducts easily accessible in peripheral blood, mainly including circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) that are shed into the blood from the tumor sites. In this review, we focus on the recent developments in the field of “liquid biopsy” as well as the diagnostic and prognostic significance of CTCs and cfNAs in HCC patients.

Performance of different biomarkers for the management of hepatocellular carcinoma

“…. Numerous studies have shown the potential utility of circulating cancer byproducts detection from which we could extract molecular information about primary tumors [51][52][53][54] . The liquid biopsy could be conducted in repeated samples providing accessible, accurate and dynamic information to evaluate the tumor status.…”

“…The liquid biopsy could be conducted in repeated samples providing accessible, accurate and dynamic information to evaluate the tumor status. These novel biomarkers are thought to have great potential and could provide individualized decision-making during HCC treatment, including the follow-up period; risk assessment, early cancer detection, treatment response or even prognostic outcome [53][54][55][56] .…”

“…CTCs are spread by tumor malignant cells into peripheral blood in order to reach distal organs and eventually develop metastatic carcinoma [54] . Several studies have analysed the role of CTCs as a marker to predict survival, recurrence or treatment response in different kinds of tumors [53,57,58] .…”

Enlarged selection criteria for hepatocellular cancer: is the upper limit needed?

“…Future criteria will probably include 'liquid biopsies' (23). This emerging concept is based on the ability to detect specific tumor DNA or cancer cells RNA (exosome) in mainstream blood (and other body fluids) (24).…”

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“…10,11 We hypothesize that increasing lesion size is associated with a change in biology or aggressiveness, and this has indeed been recently demonstrated. 12 However, other possible contributors to HCC recurrence after OLTx include immune suppression with increased tumor growth, 13,14 circulating tumor cells, [15][16][17][18] enhanced carcinogenesis in the presence of recurrent hepatitis, and patients living longer after transplant, thus having more time for preexisting micrometastases to grow.…”