Survivin-positive circulating tumor cells as a marker for metastasis of hepatocellular carcinoma

doi:10.3748/wjg.v27.i43.7546

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World Journal of Gastroenterology

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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.

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. yujings9774@sina.com.cn

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
Processing time: 179 Days and 19.6 Hours

ARTICLE HIGHLIGHTS

Research background

Circulating tumor cells (CTCs), which are also known as liquid biopsy, are mainly used as a predictor to monitor the recurrence and metastasis of tumors including hepatocellular carcinoma (HCC). Survivin is an anti-apoptotic protein that plays an important role in inhibiting apoptosis and is overexpressed in many tumors, including HCC. No study has analyzed the value of survivin-expressing CTCs in HCC.

Research motivation

We aimed to study the expression of survivin in CTCs of HCC and indicate the role of survivin-expressing CTCs as a marker for EMT and cancer progression in HCC.

Research objectives

To explore the prognostic value of survivin-expressing CTCs in HCC, and estimate survivin-positive CTCs as a potential predictor of metastasis in HCC patients.

Research methods

We examined the survivin expression patterns in CTCs of HCC patients, and investigated the in vitro effects of survivin silencing and overexpression on the proliferation and invasion of HCC cells. We also analysed the survivin protein expression in HCC tissue. And we observed the dynamic changes in survivin-positive CTC count following surgery and its prognostic significance.

Research results

The CTC and survivin-positive CTC counts were significantly higher in the HCC patients than in the normal controls. Further, survivin overexpression was found to induce HepG2 cell proliferation, reduce apoptosis, and improve invasive ability. Additionally, log-rank test revealed that the recurrence free survival rate was significantly associated with survivin-positive CTC count.

Research conclusions

Survivin-positive CTCs are promising as a predictor of HCC prognosis and metastasis.

Research perspectives

The dynamic monitoring of survivin-positive CTC count would help clinical therapy and improve the prognosis of HCC patients.