71P - Relevance of glycosylation-associated genes for tumor progression and metastasis localization in breast cancer

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Breast Cancer, Metastatic
Translational Research
Presenter Leticia Oliveira-Ferrer
Citation Annals of Oncology (2015) 26 (suppl_3): 15-24. 10.1093/annonc/mdv117
Authors L. Oliveira-Ferrer1, T. Karius1, I. Witzel1, T. Karn2, R.M. Wirtz3, V. Müller1, K. Milde-Langosch1
  • 1Department Of Gynecology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg - Hamburg/DE
  • 2Obstetrics And Gynecology, Universitätsklinikum Frankfurt(Johannes-Wolfgang Goethe Institute), 60590 - Frankfurt am Main/DE
  • 3Molecular Pathology Gmbh, STRATIFYER, Köln/DE

Abstract

Body

Glycosylation has deep impact on the stability and functional properties of proteins, and changes in glycan structures have been early detected in various malignancies including breast cancer. However, there is only limited information about their role in tumor progression and metastasis. Therefore, we analyzed the expression and prognostic value of glycosylation genes in mammary carcinomas and further investigated whether the expression of certain glycosylation genes correlated with metastasis to specific organ sites. Univariate and multivariate Cox regression analysis with 202 glycosylation genes based on their mRNA expression data were performed in a cohort of 194 mammary carcinomas. 24 glycosylation-associated genes with independent prognostic value could be identified and were further validated in a second cohort (n = 200). From the six genes showing prognostic significance in both cohorts, RPN1, FUCA1, MAN1A1 and POFUT1 were also analyzed at the protein level by western blot analysis in ca. 100 tumour samples. Here, the unfavorable prognostic value of RPN1 and a significant association with an aggressive tumour phenotype could be corroborated. Further on, high MAN1A1 mRNA and protein (52-60 kDa) expression is associated with favorable tumor parameters and better prognosis, whereas the presence of a high-molecular-weight MAN1A1 form (72 kDa) correlates with shorter survival. The significant correlation of POFUT1 expression with longer overall survival could be validated at the protein level in the group of ER-positive patients, but showed no impact on prognosis of ER-negative tumors. At mRNA level we found significant correlations of gene expression with distant metastases in general, but also with metastasis to specific organ sites. Interestingly, tumors metastasizing to the brain showed significantly more hyaluronan synthase (HAS2), but also hyaluronidase (HYAL1), indicating a vivid hyaluronan metabolism in these cases. Our data show a prognostic role of glycosylation enzymes for breast cancer patients. Correlation of gene expression with metastases of various localizations points to a role of certain glycan structures in organ-specific metastatic spread.

Disclosure: All authors have declared no conflicts of interest.