4.7 Article

Serum N-glycome alterations in breast cancer during multimodal treatment and follow-up

Journal

MOLECULAR ONCOLOGY
Volume 11, Issue 10, Pages 1361-1379

Publisher

WILEY
DOI: 10.1002/1878-0261.12105

Keywords

breast cancer; CRP; follow-up; inflammation; serum N-glycans; treatment

Categories

Funding

  1. European Union Seventh Framework Programme [260600]
  2. Science Foundation Ireland Starting Investigator Research Grant (SFI SIRG) [13/SIRG/2164]
  3. EU [278535]
  4. Pink Ribbon Movement and Norwegian Breast Cancer Society [11003001]
  5. Norwegian Research Council [191436/V50]
  6. K. G. Jebsen Center for Breast Cancer Research
  7. South-Eastern Norway Regional Health Authority
  8. Roche Norway
  9. Sanofi-Aventis Norway

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Using our recently developed high-throughput automated platform, N-glycans from all serum glycoproteins from patients with breast cancer were analysed at diagnosis, after neoadjuvant chemotherapy, surgery, radiotherapy and up to 3 years after surgery. Surprisingly, alterations in the serum N-glycome after chemotherapy were pro-inflammatory with an increase in glycan structures associated with cancer. Surgery, on the other hand, induced anti-inflammatory changes in the serum N-glycome, towards a noncancerous phenotype. At the time of first follow-up, glycosylation in patients with affected lymph nodes changed towards a malignant phenotype. C-reactive protein showed a different pattern, increasing after first line of neoadjuvant chemotherapy, then decreasing throughout treatment until 1 year after surgery. This may reflect a switch from acute to chronic inflammation, where chronic inflammation is reflected in the serum after the acute phase response subsides. In conclusion, we here present the first time-course serum N-glycome profiling of patients with breast cancer during and after treatment. We identify significant glycosylation changes with chemotherapy, surgery and follow-up, reflecting the host response to therapy and tumour removal.

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