Table_1_A Non-Invasive Nomogram for Preoperative Prediction of Microvascular Invasion Risk in Hepatocellular Carcinoma.docx

BackgroundMicrovascular invasion (MVI) is a significant predictive factor for early recurrence, metastasis, and poor prognosis of hepatocellular carcinoma. The aim of the present study is to identify preoperative factors for predicting MVI, in addition to develop and validate non-invasive nomogram for predicting MVI.
MethodsA total of 381 patients with resected HCC were enrolled and divided into a training cohort (n = 267) and a validation cohort (n = 114). Serum VEGF-A level was examined by enzyme-linked immunosorbent assay (ELISA). Risk factors for MVI were assessed based on univariate and multivariate analyses in the training cohort. A nomogram incorporating independent risk predictors was established and validated.
ResultThe serum VEGF-A levels in the MVI positive group (n = 198) and MVI negative group (n = 183) were 215.25 ± 105.68 pg/ml and 86.52 ± 62.45 pg/ml, respectively (P <0.05). Serum VEGF-A concentration ≥138.30 pg/ml was an independent risk factor of MVI (OR: 33.088; 95%CI: 12.871–85.057; P <0.001). Higher serum concentrations of AFP and VEGF-A, lower lymphocyte count, peritumoral enhancement, irregular tumor shape, and intratumoral artery were identified as significant predictors for MVI. The nomogram indicated excellent predictive performance with an AUROC of 0.948 (95% CI: 0.923–0.973) and 0.881 (95% CI: 0.820–0.942) in the training and validation cohorts, respectively. The nomogram showed a good model fit and calibration.
ConclusionsHigher serum concentrations of AFP and VEGF-A, lower lymphocyte count, peritumoral enhancement, irregular tumor shape, and intratumoral artery are promising markers for MVI prediction in HCC. A reliable non-invasive nomogram which incorporated blood biomarkers and imaging risk factors was established and validated. The nomogram achieved desirable effectiveness in preoperatively predicting MVI in HCC patients.

**背景** 微血管侵犯（Microvascular Invasion, MVI）是肝细胞癌（hepatocellular carcinoma, HCC）早期复发、转移及预后不良的重要预测因素。本研究旨在明确术前预测MVI的相关危险因素，并构建并验证用于预测MVI的无创列线图（nomogram）。

**方法** 本研究共纳入381例接受手术切除的肝细胞癌患者，将其分为训练队列（n=267）与验证队列（n=114）。采用酶联免疫吸附试验（enzyme-linked immunosorbent assay, ELISA）检测受试者血清血管内皮生长因子A（VEGF-A）水平。在训练队列中，通过单因素与多因素分析评估MVI的危险因素。构建纳入独立风险预测因子的列线图并进行验证。

**结果** MVI阳性组（n=198）与MVI阴性组（n=183）患者的血清VEGF-A水平分别为215.25±105.68 pg/ml和86.52±62.45 pg/ml（P<0.05）。血清VEGF-A浓度≥138.30 pg/ml是MVI的独立危险因素（比值比OR=33.088；95%置信区间CI：12.871~85.057；P<0.001）。较高的血清甲胎蛋白（Alpha-fetoprotein, AFP）与VEGF-A水平、较低的淋巴细胞计数、瘤周强化、不规则肿瘤形态及瘤内动脉均被鉴定为MVI的重要预测因子。该列线图在训练队列与验证队列中分别展现出优异的预测性能，受试者工作特征曲线下面积（Area Under the Receiver Operating Characteristic Curve, AUROC）分别为0.948（95%CI：0.923~0.973）与0.881（95%CI：0.820~0.942），且具备良好的模型拟合度与校准性。

**结论** 较高的血清AFP与VEGF-A水平、较低的淋巴细胞计数、瘤周强化、不规则肿瘤形态及瘤内动脉均可作为肝细胞癌患者MVI预测的潜在有效标志物。本研究构建并验证了一款纳入血液生物标志物与影像学危险因素的无创列线图，该列线图在术前预测肝细胞癌患者MVI方面展现出令人满意的临床效能。