Brief Article
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World J Gastroenterol. Feb 28, 2014; 20(8): 2098-2106
Published online Feb 28, 2014. doi: 10.3748/wjg.v20.i8.2098
Cancer stem cell markers correlate with early recurrence and survival in hepatocellular carcinoma
Zhe Guo, Le-Qun Li, Jing-Hang Jiang, Chao Ou, Li-Xia Zeng, Bang-De Xiang
Zhe Guo, Le-Qun Li, Jing-Hang Jiang, Bang-De Xiang, Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Chao Ou, Department of Clinical Laboratory, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Li-Xia Zeng, Department of Pathology, Tumor Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Xiang BD designed the research; Guo Z and Li LQ performed the research; Jiang JH and Guo Z evaluated the clinic records and performed the statistical analysis; Ou C and Zeng LX performed the immunohistochemistry experiment; Guo Z wrote the manuscript; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81260331; the National Science and Technology Major Project of the Ministry of Science and Technology of China, No. 2012ZX10002010001009; and the Innovation Project of Guangxi Graduate Education, No. 2011105981002M232
Correspondence to: Bang-De Xiang, PhD, Department of Hepatobiliary Surgery, Tumor Hospital of Guangxi Medical University, He Di Rd. 71, Nanning 530021, Guangxi Zhuang Autonomous Region, China. xiaopushu-213@163.com
Telephone: +86-771-5330968 Fax: +86-771-5312000
Received: September 24, 2013
Revised: November 6, 2013
Accepted: December 12, 2013
Published online: February 28, 2014
Processing time: 154 Days and 12.2 Hours
Abstract

AIM: To investigate whether expression of cancer stem cell (CSC) markers is associated with recurrence and survival in hepatocellular carcinoma (HCC) patients.

METHODS: A consecutive series of 90 HCC patients who underwent curative hepatectomy between April 2007 and April 2009 were analyzed. Of the 90 patients, 38 (42%) experienced recurrence within two years of surgery. To adjust for baseline differences between this early recurrence group and the other patients, propensity-score matching was used to generate 25 pairs of patients. Immunohistochemistry was used to compare expression of CD133, CD90, and epithelial cell adhesion molecule (EpCAM) in liver tissues from propensity score-matched patients and from 10 healthy adults. Associations of the three markers with HCC, clinicopathological characteristics, early recurrence, and survival time were explored.

RESULTS: The expression of all three CSC markers was significantly higher in HCC tissue than in healthy liver tissue (P < 0.001 for all). Among the HCC clinicopathology characteristics examined, the absence of tumor capsule was associated with CD133 expression (P = 0.005); higher histopathology grade and larger tumor size were associated with CD90 expression (P = 0.010 and 0.034, respectively); and elevated serum alpha-fetoprotein levels were associated with EpCAM expression (P = 0.021). Expression of CD90 and EpCAM was significantly higher in the early recurrence group than in other patients (P = 0.001 and 0.045, respectively), whereas CD133 expression was not significantly different between the two groups (P = 0.440). Multivariate analysis identified only CD90 expression as significantly associated with early recurrence. Log-rank analysis identified expression of both CD90 and EpCAM as significantly associated with survival time of HCC patients. Cox regression identified EpCAM expression as an independent predictor of survival time.

CONCLUSION: Expression of CD133, CD90, and EpCAM CSC markers may be linked to HCC tumor onset and/or progression. In addition, EpCAM expression is associated with shorter survival time, while CD90 expression is associated with early HCC recurrence.

Keywords: Hepatocellular carcinoma; Cancer stem cells; CD133; CD90; Epithelial cell adhesion molecule

Core tip: Cancer stem cells have been proposed as the cells responsible for initiating tumor formation, recurrence and metastasis, and liver cancer stem cells have been found to carry the surface markers CD133, CD90, and epithelial cell adhesion molecule (EpCAM). This paper addresses the clinical impact of CD133, CD90, and EpCAM in propensity score-matched patients with hepatocellular carcinoma. Our findings revealed that expression of CD133, CD90, and EpCAM may be linked to hepatocellular carcinoma (HCC) tumor onset and/or progression. In addition, EpCAM expression is associated with shorter survival time, while CD90 expression is associated with early HCC recurrence.