Monitoring neutrophil extracellular traps (NETs) related citrullinated histone H3: a novel biomarker of recurrence and metastasis in nasopharyngeal carcinoma

Abstract Objectives Blood-based biomarkers play a crucial role in tumor monitoring. However, for nasopharyngeal carcinoma with recurrence or metastasis (R/M-NPC), there is a notable scarcity of sensitive markers. Citrullinated histone H3 (H3Cit), a key marker of neutrophil extracellular traps (NETs), has been associated with the progression of various tumors. Nevertheless, its specific relationship with R/M-NPC remains poorly understood. Our study was designed to assess the potential of H3Cit as a predictor for R/M-NPC. Methods We recruited a cohort of 144 NPC patients, among which 80 (55.6 %) experienced recurrence or metastasis, while 64 (44.4 %) did not. Univariate and multivariate logistic regression analyses were employed to identify prognostic factors. H3Cit levels were measured, and a nomogram was developed by integrating H3Cit with other biomarkers. The nomogram was then validated in an independent cohort of 44 patients. Internal validation of the nomogram was performed using bootstrap resampling, and external validation was carried out in the independent cohort. Results Our analyses identified H3Cit (p<0.001, OR=4.706, 95 % CI=1.973–11.225), Lym (p=0.016, OR=0.355, 95 % CI=0.153–0.824), and FT4 (p=0.007, OR=0.228, 95 % CI=0.078–0.669) as independent prognostic factors. The calibration curves indicated excellent consistency. The C – index of the nomogram was 0.789 in the training cohort and 0.787 in the external validation cohort. The area under the curve (AUC) of the receiver operating characteristic curves (ROC) was 0.777 (p<0.001) in the training cohort and 0.787 (p=0.004) in the external validation cohort. The decision curve analysis demonstrated that the model had remarkable performance in clinical applications. Conclusions H3Cit emerges as a promising biomarker for predicting metastasis and recurrence in NPC patients. The nomogram constructed based on H3Cit and other factors exhibits high accuracy and strong clinical applicability in the early identification of R/M-NPC patients, which can contribute to timely and effective treatment strategies.