4 research outputs found
Immunoglobulin G glycosylation in patients with colorectal cancer
INTRODUCTION: Colorectal cancer (CRC) is a malignant neoplasm of the colon and the rectum. CRC is still associated with poor prognosis, low survival rate and usually relatively late diagnosis.
MATERIALS AND METHODS: We analysed IgG glycome composition in 1229 patients with CRC and 538 matching controls. Effects of surgery were evaluated in 28 patients sampled before and three times after surgery. Furthermore, IgG glycome composition was analysed in 39 plasma samples collected before initial diagnosis of CRC.
RESULTS: Clinical algorithms showed good prediction of all cause and CRC mortality. The inclusion of IgG glycan data in regression models did not lead to any statistically significant improvements in overall prediction of survival (Harrell’s C: 0.73, 0.77; AUC: 0.75, 0.79, IDI: 0.02, 0.04 respectively). However, the inclusion of IgG glycan data substantially improved the prediction of rapid progressors over clinical models in AJCC stage 4 patients (AUC 0.53 vs. 0.75, IDI 0.21). When analysing clinical characteristics among 760 patients and 538 matching controls it was found that CRC associates with decrease in IgG galactosylation, IgG sialylation and increase in core-fucosylation of neutral glycans with concurrent decrease of core fucosylation of sialylated glycans.
COCLUSION: The glycan differences among CRC patients are consistent with significantly increased IgG pro-inflammatory activity being associated with poorer CRC prognosis, especially in late stage CRC. Considering the functional relevance of IgG glycosylation for both tumor immunosurveilance and clinical efficacy of therapy with monoclonal antibodies, individual variation in IgG glycosylation may turn out to be important for prediction of disease course or the choice of therapy
THE IMPORTANCE OF IMMUNOGLOBULIN G N-GLYCANS IN COLORECTAL CANCER
Colorectal cancer (CRC) is a malignant neoplasm of the colon and the rectum. CRC is still associated with poor prognosis, low survival rate and usually relatively late diagnosis. Aims and objectives: This research aims to identify IgG N-glycans biomarkers with discriminative power to predict survival in patients with CRC. Specific aim: To analyse IgG N-glycans in 760 patients with CRC and 538 matching controls. Using recently developed high-throughput UPLC technology for IgG glycosylation analysis we analysed IgG glycome composition in 760 patients with CRC and 538 matching controls. Furthermore, IgG glycome composition was analysed in 39 plasma samples collected before initial diagnosis of CRC. When analysing clinical characteristics among patients and matching controls it was found that CRC associates with decrease in IgG galactosylation, IgG sialylation and increase in core-fucosylation of neutral glycans with concurrent decrease of core fucosylation of sialylated glycans. While a model based on age and sex did not show discriminative power (AUC=0.499), the addition of glycan variables into the model considerably increased the discriminative power of the model (AUC=0.755). Our findings suggest that genetic factors influencing glycome composition could be explored as risk factors for colorectal cancer. Finally, glyco-modifications might have relevance to tumour immune-surveilance and in predicting response to monoclonal antibodies. Considering the functional relevance of IgG glycosylation for both tumor immune-surveilance and clinical efficacy of therapy with monoclonal antibodies, individual variation in IgG glycosylation may turn out to be important for prediction of disease course or the choice of therapy
Esomeprazole use is independently associated with significant reduction of BMD: 1-year prospective comparative safety study of four proton pump inhibitors
© 2015 The Japanese Society for Bone and Mineral Research and Springer Japan Because of the efficacy of proton pump inhibitors (PPIs), their the use is increasing dramatically. The risk of adverse effects of short-term PPI therapy is low, but there are important safety concerns for potential adverse effects of prolonged PPI therapy. Findings from studies assessing the association between PPI use and bone mineral density (BMD) and/or fracture risk are contradictory. The aim of this study was to prospectively assess potential association of PPI treatment with the 12-month change in BMD of the lumbar spine, femur neck, and total hip. The study was performed in 200 PPI users and 50 PPI nonusers. Lumbar spine (L1–L4), femur neck, and total hip BMD were measured by dual-energy X-ray absorptiometry at the baseline and at 12 months. A total of 209 subjects completed the entire 12 months of the study and were included in the final analysis. A Wilcoxon signed-rank test showed that at 12 months PPI use was associated with statistically significant reductions in femur neck and total hip T scores (Z = -2.764, p = 0.005 and Z = -3.281, p = 0.001, respectively). A multiple linear regression analysis showed that only esomeprazole added significantly to the prediction of total lumbar spine and femur neck T scores (p = 0.048 and p = 0.037, respectively). Compared with the baseline, 12 months of PPI treatment resulted in lower femur neck and total hip BMD T scores. Among the four PPIs studied, esomeprazole was independently associated with significant reduction of BMD, whereas omeprazole had no effects on BMD. Considering the widespread use of PPIs, BMD screening should be considered in the case of prolonged PPI use