ABSTRACT
This study examines the intricate relationship between protein glycosylation dynamics and therapeutic responses in Luminal A and Luminal B breast cancer subtypes, focusing on anastrozole and tamoxifen impacts. The present methods inadequately monitor and forecast patient reactions to these treatments, leaving individuals vulnerable to the potential adverse effects of these medications. This research investigated glycan structural changes by following patients for up to 9 months. The protocol involved a series of automated steps including IgG isolation, protein denaturation, glycan labelling, purification, and final analysis using capillary gel electrophoresis with laser-induced fluorescence. The results suggested the significant role of glycan modifications in breast cancer progression, revealing distinctive trends in how anastrozole and tamoxifen elicit varied responses. The findings indicate anastrozole's association with reduced sialylation and increased core fucosylation, while tamoxifen correlated with increased sialylation and decreased core fucosylation. These observations suggest potential immunomodulatory effects: anastrozole possibly reducing inflammation and tamoxifen impacting immune-mediated cytotoxicity. This study strongly emphasizes the importance of considering specific glycan traits to comprehend the dynamic mechanisms driving breast cancer progression and the effects of targeted therapies. The nuanced differences observed in glycan modifications between these two treatments underscore the necessity for further comprehensive research aimed at thoroughly evaluating the long-term implications and therapeutic efficacy for breast cancer patients.
ABSTRACT
This study aimed to identify and quantify the clinical significance of the HE4 and ROMA index in patients with an adnexal tumour. We recruited 159 women and the HE4 and CA125 were measured with an electrochemiluminescence immunoassay in the sera. We used the Kolmogorov-Smirnov test, Mann-Whitney's test and logistic regression to interpret the data. In the premenopausal group (n = 57), the ROC analysis (with cut-off: 86.1 pmol/L for HE4; 40.7 U/L for CA125 and 21.9% for ROMA) demonstrated the superior prognostic potential of those markers when the higher cut-offs used are compared to producers. The AUC for HE4/CA125/ROMA were 0.846/0.867/0.846, respectively. The HE4/ROMA showed 85.7% sensitivity and 94% specificity. In the postmenopausal group (n = 102), the ROC analysis cut-off values were: 99.8 pmol/L for HE4; 45.8 U/L for CA125 and 38.4% for ROMA. AUC for HE4/CA125/ROMA were 0.928/0.899/0.927, respectively. HE4 had an 86.1% sensitivity at 92.4% specificity, while ROMA showed an 88.9% sensitivity at a 90.9% specificity. Impact Statement What is already known on this subject? The incidence of ovarian cancer has been increasing, despite the improvement of diagnostic, operative and therapeutic procedures. As a part of the multiparametric approach, the HE4 and ROMA index improve the diagnostic sensitivity and specificity of CA125 in the detection of ovarian cancer. What the results of this study add? The evaluation of HE4 and ROMA efficacy in the preoperative stratification was made by logistic regression analysis. The better prognostic potential of ROMA index, in patients with present adnexal mass, was obtained using our higher cut-offs for the ROMA index (21.9% for premenopausal and 38.4% for postmenopausal) in comparison to the producer's (11.7% for premenopausal and 29.9% for postmenopausal). The HE4 and ROMA index had 14.29 +LR, 0.15 -LR, 67% PPV and 97.9% NPV in the premenopausal patients. In the postmenopausal group, the HE4 had 11.37 +LR, 0.15 -LR, 75.6% PPV and 92.4% NPV, the ROMA showed 9.78 +LR, 0.12 -LR, 91.2% PPV and 95.2% NPV. What the implications are of these findings for clinical practice and/or further research? Application of a higher cut-off for HE4/CA125/ROMA index can significantly reduce the percentage of FP and FN in the preoperative stratification of ovarian cancer and justify speculations about this subject in the future.
