Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Jul 11;14(14):3373.
doi: 10.3390/cancers14143373.

Clinical Implication of Circulating Tumor Cells Expressing Epithelial Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) Markers and Their Perspective in HCC: A Systematic Review

Santhasiri Orrapin  1 , Sasimol Udomruk  1   2 , Worakitti Lapisatepun  3 , Sutpirat Moonmuang  1 , Areerak Phanphaisarn  2 , Phichayut Phinyo  2   4   5 , Dumnoensun Pruksakorn  1   2 , Parunya Chaiyawat  1   2
Affiliations
Review

Clinical Implication of Circulating Tumor Cells Expressing Epithelial Mesenchymal Transition (EMT) and Cancer Stem Cell (CSC) Markers and Their Perspective in HCC: A Systematic Review

Santhasiri Orrapin et al. Cancers (Basel). .

Abstract

Circulating tumor cells (CTCs) play a key role in hematogenous metastasis and post-surgery recurrence. In hepatocellular carcinoma (HCC), CTCs have emerged as a valuable source of therapeutically relevant information. Certain subsets or phenotypes of CTCs can survive in the bloodstream and induce metastasis. Here, we performed a systematic review on the importance of epithelial-mesenchymal transition (EMT)-CTCs and circulating cancer stem cells (CCSCs) in metastatic processes and their prognostic power in HCC management. PubMed, Scopus, and Embase databases were searched for relevant publications. PRISMA criteria were used to review all studies. Twenty publications were eligible, of which 14, 5, and 1 study reported EMT-CTCs, CCSCs, and both phenotypes, respectively. Most studies evaluated that mesenchymal CTCs and CCSCs positivity were statistically associated with extensive clinicopathological features, including larger size and multiple numbers of tumors, advanced stages, micro/macrovascular invasion, and metastatic/recurrent disease. A preliminary meta-analysis showed that the presence of mesenchymal CTCs in pre- and postoperative blood significantly increased the risk of early recurrence. Mesenchymal-CTCs positivity was the most reported association with inferior outcomes based on the prognosis of HCC recurrence. Our finding could be a step forward, conveying additional prognostic values of CTC subtypes as promising biomarkers in HCC management.

Keywords: circulating tumor cells; liquid biopsy; liver cancer; phenotypic subtype; prognostic biomarker; systematic review.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 3
Figure 3
Pooled HRs of preoperative mesenchymal CTCs (a), preoperative epithelial CTCs (b), and postoperative mesenchymal CTCs (c) subtype for the predictive risk factor of early recurrence [25,26,31,32].
Figure 1
Figure 1
Flowchart of the literature search and selection process applied according to PRISMA statement.
Figure 2
Figure 2
Venn diagram and illustration representing the results of our systematical search according to blood collection time and CTC subtypes. (E: epithelial CTCs; H: hybrid CTCs; M: mesenchymal CTCs; CSC: cancer stem cell) [19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. Created with BioRender.com, accessed on 23 May 2022.
See this image and copyright information in PMC

References

    1. Sung H., Ferlay J., Siegel R.L., Laversanne M., Soerjomataram I., Jemal A., Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021;71:209–249. doi: 10.3322/caac.21660. - DOI - PubMed
    1. Heller M., Parikh N.D., Fidelman N., Owen D. Frontiers of therapy for hepatocellular carcinoma. Abdom. Radiol. 2021;46:3648–3659. doi: 10.1007/s00261-021-03065-0. - DOI - PubMed
    1. El-Khoueiry A.B., Sangro B., Yau T., Crocenzi T.S., Kudo M., Hsu C., Kim T.-Y., Choo S.-P., Trojan J., Welling T.H., et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): An open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389:2492–2502. doi: 10.1016/S0140-6736(17)31046-2. - DOI - PMC - PubMed
    1. Zhu A.X., Finn R.S., Edeline J., Cattan S., Ogasawara S., Palmer D., Verslype C., Zagonel V., Fartoux L., Vogel A., et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): A non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19:940–952. doi: 10.1016/S1470-2045(18)30351-6. - DOI - PubMed
    1. Finn R.S., Qin S., Ikeda M., Galle P.R., Ducreux M., Kim T.-Y., Kudo M., Breder V., Merle P., Kaseb A.O., et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 2020;382:1894–1905. doi: 10.1056/NEJMoa1915745. - DOI - PubMed

LinkOut - more resources