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Circulating Tumor Cells Undergoing the Epithelial–Mesenchymal Transition: Influence on Prognosis in Cytokeratin 19-Positive Hepatocellular Carcinoma

Authors Zhang Q, Xing W, Zhang J, Hu J, Qi L, Xiang B

Received 22 December 2020

Accepted for publication 15 February 2021

Published 2 March 2021 Volume 2021:14 Pages 1543—1552


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Federico Perche

Qian Zhang,1,2,* Wanting Xing,1,2,* Jie Zhang,1,2 Junwen Hu,1,2 Lunan Qi,1– 3 Bangde Xiang1– 3

1Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumors, Ministry of Education, Nanning, People’s Republic of China; 3Guangxi Liver Cancer Diagnosis and Treatment Engineering and Technology Research Center, Nanning, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Bangde Xiang; Lunan Qi
Department of Hepatobiliary Surgery, Guangxi Medical University Cancer Hospital, 71# Hedi Road, Qingxiu District, Nanning, Guangxi, 530021, People’s Republic of China
Tel +86-7715301253; +86-13517886990
Email [email protected]; [email protected]

Purpose: The purpose of this study was to elucidate the relationship between cytokeratin 19 (CK19) expression and levels of circulating tumor cells (CTCs) in preoperative peripheral blood of patients with hepatocellular carcinoma (HCC), and the potential influence of that relationship on prognosis.
Patients and Methods: CanPatrol™ CTC-enrichment technique and in situ hybridization (ISH) were used to enrich and classify CTCs undergoing the epithelial–mesenchymal transition (EMT) from blood samples of 105 HCC patients. CK19 immunohistochemistry staining was performed on HCC tissues and compared with demographic and clinical data.
Results: In total, 27 of 105 (25.7%) HCC patients were CK19-positive. CK19-positive patients had significantly lower median tumor-free survival (TFS) than CK19-negative patients (5 vs 10 months, P = 0.047). In total, 98 (93.3%) patients showed pre-surgery peripheral blood CTCs (range: 0– 76, median: 6), and 57 of 105 (54.3%) patients displayed CTC counts ≥ 6. Furthermore, CK19-positive patients with CTC count ≥ 6 showed significantly higher percentage than CK19-negative ones (77.8% vs 46.2%, P = 0.004). CK19-positive patients showed a significantly higher proportion of mesenchymal CTCs among CTCs undergoing EMT than CK19-negative patients (mean rank: 62.28 vs 49.79, P = 0.046). We also found that CK19-positive patients with high CTC count showed significantly shorter median tumor-free survival than CK19-negative patients with low CTC count (5 vs 16 months, P = 0.039).
Conclusion: High CTC count and high percentage of mesenchymal CTCs are closely related to the expression of CK19, which is associated with poor prognosis in HCC patients.

Keywords: hepatocellular carcinoma, cytokeratin 19, circulating tumor cells, prognosis, tumor-free survival

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