Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2021; 27(43): 7546-7562
Published online Nov 21, 2021. doi: 10.3748/wjg.v27.i43.7546
Survivin-positive circulating tumor cells as a marker for metastasis of hepatocellular carcinoma
Jing Yu, Zhan Wang, Hua Zhang, Yi Wang, Dong-Qing Li
Jing Yu, Blood Transfusion Department, Wuhan Chinese and Western Medicine Hospital, Wuhan 430022, Hubei Province, China
Zhan Wang, Yi Wang, Laboratory, Tianjin Hospital, Tianjin 300211, China
Hua Zhang, Laboratory, Guoyao Dongfeng Hospital, Shiyan 442008, Hubei Province, China
Dong-Qing Li, Department of Microbiology, School of Basic Medical Sciences, Wuhan University, Wuhan 430000, Hubei Province, China
Author contributions: Yu J and Wang Z contributed equally to this work; Yu J and Wang Z had access to all the clinical data generated by the study and take responsibility for data integrity and accuracy of the data analysis; Yu J conceptualized and designed the study; Zhang H and Wang L contributed to acquisition, analysis, or interpretation of the data; Yu J and Wang Z contributed to manuscript preparation; Li DQ supervised the study.
Supported by the National Natural Science Foundation of China, No. 81772839; and the Health and Family Planning Commission Foundation of Hubei Province, No. WJ2019H194.
Institutional review board statement: The study was approved by the ethics committee of Hubei Cancer Hospital (Ethical approval number: LLHBCH2019LW-002).
Conflict-of-interest statement: The authors declare no conflicts of interest for this study.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Jing Yu, PhD, Associate Chief Technician, Doctor, Blood Transfusion Department, Wuhan Chinese and Western Medicine Hospital, No. 215 Zhongshan Road, Wuhan 430022, Hubei Province, China.
Received: May 23, 2021
Peer-review started: May 23, 2021
First decision: June 12, 2021
Revised: July 19, 2021
Accepted: October 27, 2021
Article in press: October 27, 2021
Published online: November 21, 2021

Circulating tumor cells (CTCs) and survivin are indicators for tumor stage and metastasis, as well as epitheliomesenchymal transition, in various cancers, including hepatocellular cancer (HCC).


To explore the potential of survivin-positive CTCs, specifically, as a marker for tumor progression in HCC patients.


We examined the survivin expression pattern in CTCs obtained from 179 HCC patients, and investigated the in vitro effects of survivin silencing and overexpression on the proliferation and invasion of HCC cells. CTC count and survivin expression in patient samples were examined using RNA in situ hybridization.


All 179 patients were positive for CTC markers, and 94.41% of the CTCs were positive for survivin. The CTC and survivin-positive CTC counts were significantly higher in the HCC patients than in the normal controls, and were significantly associated with tumor stage and degree of differentiation. Further, survivin overexpression was found to induce HepG2 cell proliferation, reduce apoptosis, and improve invasive ability.


Survivin shows upregulated expression (indicative of anti-apoptotic effects) in HCC. Thus, survivin-positive CTCs are promising as a predictor of HCC prognosis and metastasis, and their accurate measurement may be useful for the management of this cancer.

Keywords: Survivin, Circulating tumor cells, Hepatocellular carcinoma, Prognosis, Metastasis

Core Tip: This study first analyzed surviving-positive circulating tumor cells (CTCs) in patients with hepatocellular carcinoma (HCC). The levels of survivin expression in different CTCs were significantly different. The rates of moderate and high expression in the mesenchymal and hybrid CTCs were significantly higher than those in the epithelial CTCs. Survivin overexpression induced HCC cell proliferation, promoted their invasive ability, and reduced apoptosis. The expression of survivin in mesenchymal CTCs (mCTCs) in liver cancer was associated with metastasis and detection of survivin positivity in mCTCs may have potential value in early detection of tumor metastasis and prognostic evaluation.