Abstract
The ectonucleotidase CD39 is pivotal in the conversion of immunostimulatory adenosine triphosphate (ATP) into immunosuppressive adenosine which potently inhibits host immune responses against cancer. This study investigated the expression level and prognostic significance of CD39 in human rectal adenocarcinoma. Our data demonstrated that CD39 staining strongly marked malignant epithelial cells where the protein and messenger RNA (mRNA) expression levels of CD39 were significantly increased compared with paracancerous controls. In addition to primary tumors, CD39 was also abundantly expressed in liver metastases and tumor-draining lymph nodes from metastatic rectal adenocarcinoma. Although patients with higher CD39 density in tumor cells were more likely to have favorable characteristics (early TNM and N stages) and overall survival, the singular parameter cannot be used as an independent factor for predicting patients’ prognosis. Intriguingly, combined analysis of CD39 and CD73 expression was more efficient to foretell patient’s outcome where patients with increased CD73 but decreased CD39 levels displayed a worst prognosis. Taken together, the current study revealed that malignant epithelial cells of human rectal adenocarcinoma strongly express CD39 that may play a potential role in the tumor invasion and metastasis. Although high expression of CD39 in tumor cells is correlated with favorable clinical outcome, the combination of CD39 and CD73 expression may have a better prognostic value.
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A special thanks to Pro. Wen Wen for his technical assistance.
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This work was supported by the Beijing Natural Science Foundation (7133254 to Bin Zhang). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Supporting Figure 1
IHC characteristics of CD39 and CD73 in human rectal adenocarcinoma. (a, b) Representative IHC images of tumoral CD39 and CD73 in the same tumor area. The digital images analyzed with the Aperio ImageScope software (×200-fold magnification). Micrograph indicates the amplified morphology of tissue. Black scale bars, 100 um. (JPEG 2716 kb)
Supporting Figure 2
The prognostic significance of combining tumoral CD39 and CD73 expression in human rectal adenocarcinoma. (a, b, c) The OS rates of patients with high (above median) or low (below median) CD39 and CD73 levels in tumor cells were compared using Kaplan-Meier analysis. (GIF 62 kb)
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Zhang, B., Cheng, B., Li, FS. et al. High expression of CD39/ENTPD1 in malignant epithelial cells of human rectal adenocarcinoma. Tumor Biol. 36, 9411–9419 (2015). https://doi.org/10.1007/s13277-015-3683-9
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DOI: https://doi.org/10.1007/s13277-015-3683-9