Combined prognostic value of the cancer stem cell markers CD47 and CD133 in esophageal squamous cell carcinoma

• Published in: Cancer medicine (Malden, MA) Vol. 8; no. 3; pp. 1315 - 1325
• Main Authors: Wang, Jian‐Hua, Huang, Shu‐Ting, Zhang, Lan, Liu, Zi‐Gang, Liang, Rong‐Xin, Jiang, Sen‐Wei, Jiang, Yi‐Nan, Yu, Xing‐Juan, Jiang, Yu‐Chuan, Li, Xi‐Zhao, Zhang, Pei‐Fen, Wen, Zhe‐Sheng, Zheng, Min
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2019; John Wiley and Sons Inc
• Subjects: AC133 Antigen - genetics; AC133 Antigen - metabolism; Adult; Aged; Biomarkers, Tumor; Cancer Prevention; Cancer therapies; CD133; CD47; CD47 Antigen - genetics; CD47 Antigen - metabolism; CSCs; ESCC; Esophageal cancer; Esophageal Squamous Cell Carcinoma - diagnosis; Esophageal Squamous Cell Carcinoma - metabolism; Esophageal Squamous Cell Carcinoma - mortality; Esophageal Squamous Cell Carcinoma - therapy; Esophagus; Ethics; Female; Gene Expression; Humans; Immunoglobulins; Immunohistochemistry; Male; Medical prognosis; Middle Aged; Neoplasm Grading; Neoplasm Staging; Neoplastic Stem Cells - metabolism; Original Research; Patients; Prognosis; Proteins; Squamous cell carcinoma; Stem cells; Studies; Surgery; Survival Analysis; therapeutic; Therapeutic applications; Tumors; United States > US; China; therapeutic; CD47; prognosis; ESCC; CD133; CSCs
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1894

Background Treatments based on the inhibition of pivotal signals of cancer stem cells (CSCs) are on a promising track. Recent studies have shown that targeting CSCs with broader immune‐based therapeutic methods, for example, the anti‐CD47 treatment, may serve as a more potent strategy for eliminating these intractable cells. We aimed to explore the prognostic effects of CD47/CD133 and the potential therapeutic significance of CD47 in esophageal squamous cell carcinoma (ESCC). Methods Immunohistochemistry was employed to identify the characteristics of CD47 and CD133 in 26 pairs of tumor tissues and adjacent non‐tumor tissues and 136 ESCC tissues. Kaplan‐Meier analysis and Cox proportional hazards models were built for estimating the prognostic values of CD47 and CD133 expression and their combined stemness index. Sphere formation assays were undertaken to explore the effects of CD47 inhibition on primary human ESCC CSCs. Results Results conclude that CD47 and CD133 expression is increased in tumor tissues as compared to adjacent non‐tumor tissues. A positive correlation between CD47/CD133 expression and differentiation was found in 136 ESCC patients. Survival analysis indicated that patients with high CD47 or CD133 expression exhibited poor overall survival and progression‐free survival (PFS). The combination of high CD47 and CD133 expression was a reliable independent prognostic factor for both OS (HR = 1.940, 95% CI = 1.399‐2.690, P < 0.0001) and progression‐free survival (HR = 1.883, 95% CI = 1.384‐2.562, P < 0.0001). Notably, CD47+ CD133+ ESCC cells were observed to possess the characteristics of CSCs, and anti‐CD47 treatment veritably eliminated the CSCs pool. Conclusions The stemness index determined by the expression of CD47 and CD133 is a promising prognostic predictor, and CD47 is a potential therapeutic target for CSCs in ESCC patients. We posited that targeting Cancer Stem Cells with broader immune‐based therapeutic methods may be a more potent alternative for eradicating these problematic cells.