Background:Cervical lymph node metastases are a major prognostic factor in patients with oral squamous cell carcinoma (OSCC). Despite advances in imaging, accurate preoperative prediction of nodal involvement remains a challenge. This study evaluated the utility of Isotope Ratio Mass Spectrometry (IRMS) in assessing the risk of lymph node metastases in patients with OSCC. We hypothesize that alterations in the abundance of13C and15N stable isotopes in OSCC tumor tissues reflect metabolic reprogramming associated with tumor progression and may correlate with cervical lymph node metastases.Methods:A prospective cohort of 61 patients with primary OSCC undergoing surgical treatment was analyzed. Tumor tissue samples were evaluated for the relative abundance of nitrogen-15 (15N) and carbon-13 (13C) isotopes using IRMS. Correlations between isotopic values and nodal metastases, as well as established clinicopathological risk factors, were assessed.Results:IRMS measurements of13C and15N abundance did not directly correlate with the presence of lymph node metastases but were associated with advanced tumor stages and negative prognostic features, such as angioinvasion/neuroinvasion. The median of the average nitrogen15N content was higher in patients with more advanced clinical stages (11.89% in stage IV vs. 11.12% in stages I–III;p= 0.04‰), and the median δ13C was lower in stage IV compared to stages I–III (−22.40‰ vs. −22.88‰;p< 0.05). Patients with angioinvasion/neuroinvasion also had a lower median δ13C (−22.26‰ vs. −22.75‰;p< 0.05). These findings suggest that IRMS reflects metabolic changes in tumor biology rather than specifically predicting nodal metastases. Multivariate logistic regression identified age, gender, and clinical tumor stage as independent predictors of nodal involvement.Conclusion:IRMS-based isotopic profiling may reflect key metabolic alterations associated with OSCC progression. Although IRMS parameters of carbon13C and nitrogen15N were not independently predictive of lymph node status, they were associated with key adverse prognostic features, indicating their potential as adjunctive biomarkers that may complement traditional histopathological evaluation.
背景：颈淋巴结转移是口腔鳞状细胞癌（OSCC）患者的主要预后因素。尽管影像学技术有所进步，但术前准确预测淋巴结受累仍具挑战。本研究评估了同位素比值质谱法（IRMS）在评估OSCC患者淋巴结转移风险中的应用价值。我们假设OSCC肿瘤组织中碳13（13C）和氮15（15N）稳定同位素丰度的变化反映了与肿瘤进展相关的代谢重编程，并可能与颈淋巴结转移相关。 方法：对61例接受手术治疗的原发性OSCC患者进行前瞻性队列分析。采用IRMS检测肿瘤组织中氮15（15N）和碳13（13C）同位素的相对丰度。评估同位素值与淋巴结转移及已知临床病理危险因素之间的相关性。 结果：IRMS测定的13C和15N丰度与淋巴结转移的存在无直接相关性，但与晚期肿瘤分期及血管侵犯/神经侵犯等不良预后特征相关。临床分期更晚的患者中，平均氮15N含量的中位数更高（IV期为11.89% vs I–III期为11.12%；p=0.04‰），而IV期患者的δ13C中位数低于I–III期（−22.40‰ vs −22.88‰；p<0.05）。存在血管侵犯/神经侵犯的患者δ13C中位数也较低（−22.26‰ vs −22.75‰；p<0.05）。这些发现表明IRMS反映的是肿瘤生物学中的代谢变化，而非特异性预测淋巴结转移。多因素逻辑回归分析确定年龄、性别和临床肿瘤分期为淋巴结受累的独立预测因素。 结论：基于IRMS的同位素谱分析可能反映与OSCC进展相关的关键代谢改变。尽管碳13C和氮15N的IRMS参数不能独立预测淋巴结状态，但它们与关键不良预后特征相关，表明其具有作为辅助生物标志物的潜力，可补充传统的组织病理学评估。
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