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Page 14 of 18 Malentacchi et al. J Cancer Metastasis Treat 2020;6:34 I http://dx.doi.org/10.20517/2394-4722.2020.34

As discussed in this review, the investigation of biomarkers in LB of EC evidenced that only experimental
approaches have been proposed, and none of them have reached clinical application. In particular, most of
the results concerning LB in EC are referred to circulating cell free DNA/ctDNA and CTCs in blood. This
fact may be related to the statement that most ECs have a good prognosis and are diagnosed at early stage,
and thus little effort has been made in this direction despite the improvement of new technologies (e.g.,
NGS and ddPCR) and new isolation systems for emerging biospecimen for LB in cancer detection (e.g.,
CTC and EV) The overview of LB biomarkers in EC shows that blood is the most investigated biospecimen
and the main biomolecules are miRNA and ctDNA. Nevertheless, for those biomarkers evaluated in EC,
some discrepancies were observed among studies, mainly related to the lack of standard procedures for
pre-analytical and analytical phases. This aspect plays a critical role in EC, principally due to the limited
number of studies or patients recruited within each study performed on this topic. Nevertheless, to
underline the efforts performed in this direction, in this review, we present, albethey isolated, studies that
for the first time performed analyses of specific biomarkers in LB of EC (e.g., circulating mRNA in blood)
and we provocatively suggest to extend them to biomarkers (lncRNA, methylation of circulating miRNA,
and single CTC analysis) not yet analyzed in EC but investigated in other cancers. The purpose is to suggest
that LB of EC represents a fascinating tool and field of study to improve the knowledge of this type of
tumor and to improve the life-quality of patients.

DECLARATIONS
Authors’ contributions
Made substantial contributions to conception and design of the study: Malentacchi F, Pillozzi S
Data research: Malentacchi F, Sgromo C
Revision of the manuscript: Antonuzzo L

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
All authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2020.

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