J Cancer 2020; 11(14):4240-4249. doi:10.7150/jca.33699 This issue

Research Paper

Prognostic value of stem cell markers in esophageal and esophagogastric junction cancer: a meta-analysis

Elisabetta Trevellin1✉, Giovanni Pirozzolo2, Matteo Fassan3, Roberto Vettor1

1. Department of Medicine, Endocrine-Metabolic Laboratory, University of Padua, 35128 Padua, Italy
2. Emergency General Surgery, Ospedale dell'Angelo - ULSS 3 Serenissima, 30174 Venice, Italy
3. Department of Medicine, Surgical Pathology Unit, University of Padua, 35128 Padua, Italy

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Trevellin E, Pirozzolo G, Fassan M, Vettor R. Prognostic value of stem cell markers in esophageal and esophagogastric junction cancer: a meta-analysis. J Cancer 2020; 11(14):4240-4249. doi:10.7150/jca.33699. Available from https://www.jcancer.org/v11p4240.htm

File import instruction


Background: Esophageal cancer is an aggressive tumor, with poor prognosis and low survival rates. Although diagnosis and treatment have improved considerably, more efficient prognostic factors are urgently needed to prevent postoperative recurrence and metastasis. Cancer stem cells are key players in tumor progression and several studies have investigated the association between the expression of stemness genes and clinical outcome. However, the prognostic value of stemness markers in esophageal cancer remains controversial. We identified six factors involved in angiogenesis, anti-apoptosis and self-renewal that have been associated to poor prognosis in other types of cancer. We conducted a review of the literature and a meta-analysis to assess their potential prognostic role in this malignancy.

Material and Methods: The database of PMC, PubMed, Web of Science, Embase and The Cochrane Library were searched to investigate the association between CD34, CD133, Nucleostemin, OCT-4, NANOG and CD90, and the survival of patients affected by esophageal squamous cell carcinoma or esophageal adenocarcinoma. Among the 615 eligible studies, a total of 19 articles (including 1586 patients) met the inclusion criteria for the meta-analysis, and the pooled hazard ratio and 95% confidence intervals were calculated.

Results: Data showed that high expression of CD34 (HR 2.10; 95%CI 1.41-3.14; I2=56%; p=0.0003), CD133 (HR 1.91; 95%CI 1.15-3.19; I2=55%; p=0.01) and Nucleostemin (HR 2.97; 95%CI 1.11-7.98; I2=0%; p=0.03) were associated with poor prognosis in patients affected by esophageal cancer. The expression of NANOG and OCT-4 showed no significant association with survival of patients, whereas no study involving CD90 was included in this meta-analysis. Conclusion: CD34, CD133 and Nucleostemin might represent useful prognostic markers in patients affected by esophageal cancer.

Keywords: Esophageal cancer, Cancer stem cells, CD34, CD133, Nucleostemin, Neoadjuvant therapy, Prognosis