Liquid biopsy for the assessment of adrenal cancer heterogeneity: where do we stand?

Abstract

Almost 10 years have passed since the first attempts of liquid biopsy aimed at the characterisation of tumor cells present in the bloodstream from a regular sample of peripheral blood were performed. Liquid biopsy has been used to characterise tumor heterogeneity in various types of solid tumors including adrenocortical carcinoma. The development of molecular biology, genetics, and methodological advances such as digital PCR and next-generation sequencing allowed us to use besides circulating tumor cells a variety of circulating cell-free nucleic acids, DNAs, RNAs and microRNAs secreted by tumors into blood and other body fluids as specific molecular markers. These markers are used for diagnosis, to check tumor development, selecting efficient therapies, therapy monitoring and even possess prognostic power. In adrenocortical carcinoma, there are some studies reporting analysis of circulating tumor cells, circulating cell free DNA and microRNAs for assessing tumor heterogeneity. Among microRNAs, hsa-miR-483-5p seems to be the most important player. Combined with other microRNAs like hsa-miR-195, their expression correlates with recurrence-free survival. Most studies support the applicability of liquid biopsy for assessing temporal tumor heterogeneity (i.e. tumor progression) in adrenocortical cancer. In this mini-review, the available findings of liquid biopsy for assessing tumor heterogeneity in adrenocortical cancer are presented.

Review of Diagnostic Modalities for Adrenal Incidentaloma

“…The use of liquid biopsies (LB) to diagnose ACC involves detecting neo cells and "cell-free" nucleic acids (DNA, RNA, and microRNA) that are derived from the tumor and released into the blood and other body fluids using modern molecular techniques such as PCR and next-generation sequencing [31].…”

“…Circulating tumor DNA (ctDNA) is another marker that can be relevant in noninvasive diagnostics of different types of cancer [31]. A higher amount of ctDNA was found in advanced stages of different cancers in relation to locoregional stages [33].…”

“…A higher amount of ctDNA was found in advanced stages of different cancers in relation to locoregional stages [33]. However, the number of studies evaluating the usefulness of ctDNA in patients with ACC is small, and the study groups are insufficient to draw clear conclusions [31]. Creemers et al detected tumor-specific ctDNA mutations in only one of three patients with mutations in primary ACC (the study group consisted of six patients) [34].…”

“…While LB shows promise, it is still in the early stages and requires further research, especially in the context of ACC diagnosis [31].…”

Eighth International Adrenal Cancer Symposium Brescia, Italy, September 30 to October 1–2, 2021

“…Perge et al [4] reviewed the available findings of liquid biopsy for assessing tumor heterogeneity in adrenocortical cancer. The authors pointed out that the investigation of markers of tumor heterogeneity in adrenocortical cancer is in the preliminary phase, but the few available studies provided some encouraging results.…”