NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training, Dublin, Ireland.
Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, Norway.
Mol Oncol. 2017 Oct;11(10):1361-1379. doi: 10.1002/1878-0261.12105. Epub 2017 Jul 24.
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.
利用我们最近开发的高通量自动化平台，在诊断时、新辅助化疗后、手术、放疗以及手术后长达 3 年内，分析了来自乳腺癌患者所有血清糖蛋白的 N-聚糖。令人惊讶的是，化疗后血清 N-聚糖的改变具有促炎作用，与癌症相关的聚糖结构增加。另一方面，手术诱导了血清 N-聚糖的抗炎变化，向非癌表型转变。在首次随访时，淋巴结受影响的患者的糖基化向恶性表型转变。C 反应蛋白表现出不同的模式，在一线新辅助化疗后增加，然后在整个治疗过程中直至手术后 1 年逐渐减少。这可能反映了从急性炎症向慢性炎症的转变，其中慢性炎症在急性炎症反应消退后反映在血清中。总之，我们首次在乳腺癌患者治疗期间和治疗后进行了时间过程血清 N-聚糖谱分析。我们发现了化疗、手术和随访过程中的显著糖基化变化，反映了宿主对治疗和肿瘤切除的反应。
