Table_1_VEGF-D Serum Level as a Potential Predictor of Lymph Node Metastasis and Prognosis in Vulvar Squamous Cell Carcinoma Patients.docx

BackgroundRadical surgical resection of the primary tumor with mono/bilateral inguinofemoral lymph node dissection is the standard treatment for invasive vulvar squamous cell carcinoma (VSCC) and is frequently related to severe morbidity. Tailoring surgical treatment is of paramount importance, and a comprehensive preoperative evaluation is mandatory. Vascular endothelial growth factor D (VEGF-D) is considered a regulator of lymphangiogenesis involved in tumor spread via lymphatic vessels. The aim of this study was to evaluate the potential of VEGF-D in the prediction of inguinofemoral lymph node metastasis.
MethodsWe analyzed the preoperative levels of serum VEGF-D (sVEGF-D) from two independent cohorts of patients with VSCC by enzyme-linked immunosorbent assay and its protein expression on tumor tissue by immunohistochemistry. Logistic regression was performed to identify the independent risk factors for lymph node metastasis, and Cox proportional hazard model was used for survival analysis.
ResultsHigh levels of sVEGF-D, but not tissue VEGF-D, significantly correlated with positive groin nodes and a more advanced International Federation of Gynecologists and Obstetricians (FIGO) stage. In multivariable analysis, a high sVEGF-D level was an independent predictor of lymph node metastasis and worse prognosis. A prediction model based on sVEGF-D, tumor grade assessed on biopsy, tumor diameter, and lymph node clinical evaluation was able to predict lymph node metastasis, reaching C-index values of 0.79 and 0.73 in the training and validation cohorts, respectively.
ConclusionsThe preoperative sVEGF-D level might be a reliable biomarker for the prediction of lymph node metastasis and prognosis in patients with VSCC, supporting better clinical/surgical decision. Multicenter prospective studies are required to confirm our findings.

背景：侵袭性外阴鳞状细胞癌（invasive vulvar squamous cell carcinoma, VSCC）的标准治疗方案为原发肿瘤根治性切除术联合单侧/双侧腹股沟股淋巴结清扫术，但该术式常伴随严重术后并发症。个体化定制手术方案至关重要，全面的术前评估亦必不可少。血管内皮生长因子D（Vascular endothelial growth factor D, VEGF-D）被认为是淋巴管生成的调节因子，参与肿瘤经淋巴道的播散。本研究旨在评估VEGF-D在预测腹股沟股淋巴结转移中的应用潜力。
方法：本研究通过酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）检测了两个独立VSCC患者队列的术前血清VEGF-D（serum VEGF-D, sVEGF-D）水平，并采用免疫组织化学法检测其在肿瘤组织中的蛋白表达情况。通过Logistic回归分析确定淋巴结转移的独立危险因素，并使用Cox比例风险模型开展生存分析。
结果：血清VEGF-D水平升高（而非组织VEGF-D）与腹股沟淋巴结阳性及更高的国际妇产科联盟（International Federation of Gynecologists and Obstetricians, FIGO）分期显著相关。多变量分析显示，高水平sVEGF-D是淋巴结转移及不良预后的独立预测因子。基于sVEGF-D、活检肿瘤分级、肿瘤直径及淋巴结临床评估构建的预测模型可有效预测淋巴结转移，在训练队列与验证队列中的C指数分别达到0.79与0.73。
结论：术前sVEGF-D水平可作为预测VSCC患者淋巴结转移及预后的可靠生物标志物，有助于优化临床与手术决策。未来需开展多中心前瞻性研究以验证本研究结果。