Correlation of GD2 Biosynthesis Enzymes With Cancer Stem Cell Markers in Human Breast Cancer.

Abstract

Background/aim: The disialoganglioside GD2 has been shown to promote cell proliferation, migration, tumor and metastasis through specific signaling pathways in tumor cells originating from the neuroectoderm, including melanomas, neuroblastomas, glioblastomas, and breast carcinomas. GD2 has therefore emerged as a potential diagnostic biomarker in early malignancy as evidenced by the high specificity of its expression in tumor cells. Furthermore, recent findings show that GD2 might also act as a novel cancer stem cell (CSC) marker. Our study aimed to investigate the relationship between GD2 and 34 recognized CSC markers in human breast cancer.

Materials and methods: We analyzed the relationship between the mRNA expression profiles of three key enzymes involved in the biosynthesis of GD2 - B4GalT5, B4GALNT1, and ST8SIA1 - and 34 CSC markers in 91 human breast cancer tissue samples.

Results: All three enzymes had positive and statistically significant correlation between each other with p<0.0001. Furthermore, each enzyme was found to have highly significant correlations with 15 CSC markers associated with aggressive cancer behavior: BMI1, CX43, ALCAM (CD166), Podoplanin, CD29, CD24, CD49f, IL8RA, NGFR, hTERT, Nestin, OCT4, CTBP, PSCA and Myc.

Conclusion: These findings lend further support to the growing evidence that GD2 is a potential biomarker of CSCs and epithelial-mesenchymal transition (EMT) in human breast cancer that can be amenable to therapeutic targeting.