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Finding the seed of recurrence: Hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment.

ABSTRACT: The treatment for hepatocellular carcinoma (HCC) relies on liver resection, which is, however, burdened by a high rate of recurrence after surgery, up to 60% at 5 years. No pre-operative tools are currently available to assess the recurrence risk tailored to every single patient. Recently liquid biopsy has shown interesting results in diagnosis, prognosis and treatment allocation strategies in other types of cancers, since its ability to identify circulating tumor cells (CTCs) derived from the primary tumor. Those cells were advocated to be responsible for the majority of cases of recurrence and cancer-related deaths for HCC. In fact, after being modified by the epithelial-mesenchymal transition, CTCs circulate as "seeds" in peripheral blood, then reach the target organ as dormant cells which could be subsequently "awakened" and activated, and then initiate metastasis. Their presence may justify the disagreement registered in terms of efficacy of anatomic vs non-anatomic resections, particularly in the case of microvascular invasion, which has been recently pointed as a histological sign of the spread of those cells. Thus, their presence, also in the early stages, may justify the recurrence event also in the contest of liver transplant. Understanding the mechanism behind the tumor progression may allow improving the treatment selection according to the biological patient-based characteristics. Moreover, it may drive the development of novel biological tailored tests which could address a specific patient to neoadjuvant or adjuvant strategies, and in perspective, it could also become a new method to allocate organs for transplantation, according to the risk of relapse after liver transplant. The present paper will describe the most recent evidence on the role of CTCs in determining the relapse of HCC, highlighting their potential clinical implication as novel tumor behavior biomarkers able to influence the surgical choice.

SUBMITTER: Carissimi F

PROVIDER: S-EPMC8462072 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCancer stem cells (CSCs) and Circulating tumor cells (CTCs) have been proposed as fundamental causes for the recurrence of hepatocellular carcinoma (HCC). CTCs isolated from patients with HCC illustrate a unique Nanog expression profile analysis. The aim of this study was to enhance the prediction of recurrence and prognosis of the CTC phenotype in patients with HCC by combining Nanog expression into a combined forecasting model.Subjects materials and methodsWe collected 320 blood samples from 160 patients with HCC cancer before surgery and used CanPatrol™ CTC enrichment technology and in situ hybridization (ISH) to enrich and detect CTCs and CSCs. Nanog expression in all CTCs was also determined. In addition, RT-PCR and immunohistochemistry were used to study the expression of Nanog, E-Cadherin, and N-Cadherin in liver cancer tissues and to conduct clinical correlation studies.ResultsThe numbers of EpCAM mRNA+ CTCs and Nanog mRNA+ CTCs were strongly correlated with postoperative HCC recurrence (CTC number (P = 0.03), the total number of mixed CTCS (P = 0.02), and Nanog> 6.7 (P = 0.001), with Nanog > 6.7 (P = 0.0003, HR = 2.33) being the most crucial marker. There are significant differences in the expression of Nanog on different types of CTC: most Epithelial CTCs do not express Nanog, while most of Mixed CTC and Mesenchymal CTC express Nanog, and their positive rates are 38.7%, 66.7%, and 88.7%, respectively, (P=0.0001). Moreover, both CTC (≤/> 13.3) and Nanog (≤/>6.7) expression were significantly correlated with BCLC stage, vascular invasion, tumor size, and Hbv-DNA (all P < 0.05). In the young group and the old group, patients with higher Nanog expression had a higher recurrence rate. (P < 0.001).ConclusionsThe number of Nanog-positive cells showed positive correlation with the poor prognosis of HCC patients. The detection and analysis of CTC markers (EpCAM and CK8, 18, CD45 Vimentin,Twist and 19) and CSCs markers (NANOG) are of great value in the evaluation of tumor progression.

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Finding the seed of recurrence: Hepatocellular carcinoma circulating tumor cells and their potential to drive the surgical treatment.

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