Background: Nodal (N) stage is one of the most important predictors for distant metastasis in nasopharyngeal carcinoma (NPC) patients. It may ignore potentially useful nodal features, such as nodal matting (three or more lymph nodes abutting together with the absence of intervening fat planes). Purpose: To explore the prognostic value of nodal matting in NPC patients and construct a nomogram with nodal matting for predicting distant metastasis-free survival (DMFS). Study type: Retrospective. Population: In all, 792 NPC patients treated with intensity modulated radiation therapy from 2010 to 2013 were enrolled with 2:1 training (n = 527) and validation (n = 65) cohorts. Field Strength/Sequence: T 1-and T 2-weighted imaging at 1.5 or 3.0T. Assessment: Nodal matting and other nodal characteristics were assessed with MRI. MR images were evaluated separately by three radiologists. The association between nodal matting and DMFS was analyzed. Statistical Tests: Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. Nomograms were constructed from a multivariate logistic regression model with and without nodal matting. The predictive accuracy and discriminative ability of the nomograms were determined by concordance index (C-index) and calibration curves. The results were validated using bootstrap resampling and validation cohort. Results: The incidence of nodal matting was 24.6% (195/792) in all patients. In the training cohort, nodal matting was independently associated with DMFS (hazard ratio [HR] = 1.97 [1.05-3.69], P < 0.05). N1 patients with nodal matting had worse DMFS than N1 patients without (P < 0.05). However, no significant difference was observed when comparing N1 patients with nodal matting to N2 patients (P = 0.464). The C-index of the nomogram with nodal matting was higher than the nomogram without (0.717 vs. 0.699, P = 0.084). Data Conclusion: Nodal matting was an independent prognostic factor for DMFS in NPC patients. It may help to select patients at high risk of distant metastasis.
Background: Bone morphogenetic protein 5 (BMP5) has been identified as one of the important risk factors for microtia; however, the link between them has yet to be clarified. In this study, we aimed to demonstrate the relationship of BMP5 with mitochondrial function and investigate the specific role of mitochondria in regulating microtia development.Methods: BMP5 expression was measured in auricular cartilage tissues from patients with and without microtia. The effects of BMP5 knockdown on cellular function and mitochondrial function were also analyzed in vitro. Changes in genome-wide expression profiles were measured in BMP5-knockdown cells.Finally, the specific impact of BMP5 down-regulation on mitochondrial fat oxidation was analyzed in vitro.Results: BMP5 expression was down-regulated in the auricular cartilage tissues of microtia patients.BMP5 down-regulation inhibited various cellular functions in vitro, including cell proliferation, mobility, and cytoactivity. The functional integrity of mitochondria was also damaged, accompanied by a decrease in mitochondrial membrane potential, reactive oxygen species (ROS) neutralization, and reduced adenosine triphosphate (ATP) production. Carnitine O-palmitoyltransferase 2 and diacylglycerol acyltransferase 2, two of the key regulators of mitochondrial lipid oxidation, were also found to be decreased by BMP5 downregulation.Conclusions: Down-regulation of BMP5 affects glycerolipid metabolism and fatty acid degradation, leading to mitochondrial dysfunction, reduced ATP production, and changes in cell function, and ultimately resulting in microtia. This research provides supporting evidence for an important role of BMP5 downregulation in affecting mitochondrial metabolism in cells, and sheds new light on the mechanisms underlying the pathogenesis of microtia.
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