Department of Radiology, West China Hospital, Sichuan University, Chengdu, China.
Big Data Research Center, University of Electronic Science and Technology of China, Chengdu, China.
Front Immunol. 2022 Aug 25;13:973153. doi: 10.3389/fimmu.2022.973153. eCollection 2022.
As a coreceptor in Wnt and HGF signaling, glypican-3 (GPC-3) promotes the progression of tumor and is associated with a poor prognosis in hepatocellular carcinoma (HCC). GPC-3 has evolved as a target molecule in various immunotherapies, including chimeric antigen receptor T cell. However, its evaluation still relies on invasive histopathologic examination. Therefore, we aimed to develop an easy-to-use and noninvasive risk score integrating preoperative gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) and clinical indicators to predict positive GPC-3 expression in HCC.
Consecutive patients with surgically-confirmed solitary HCC who underwent preoperative EOB-MRI between January 2016 and November 2021 were retrospectively included. EOB-MRI features were independently evaluated by two masked abdominal radiologists and the expression of GPC-3 was determined by two liver pathologists. On the training dataset, a predictive scoring system for GPC-3 was developed against pathology logistical regression analysis. Model performances were characterized by computing areas under the receiver operating characteristic curve (AUCs).
A total of 278 patients (training set, n=156; internal validation set, n=39; external validation set, n=83) with solitary HCC (208 [75%] with positive GPC-3 expression) were included. Serum alpha-fetoprotein >10 ng/ml (AFP, odds ratio [OR]=2.3, four points) and five EOB-MR imaging features, including tumor size >3.0cm (OR=0.5, -3 points), nonperipheral "washout" (OR=3.0, five points), infiltrative appearance (OR=9.3, 10 points), marked diffusion restriction (OR=3.3, five points), and iron sparing in solid mass (OR=0.2, -7 points) were significantly associated with positive GPC-3 expression. The optimal threshold of scoring system for predicting GPC-3 positive expression was 5.5 points, with AUC 0.726 and 0.681 on the internal and external validation sets, respectively.
Based on serum AFP and five EOB-MRI features, we developed an easy-to-use and noninvasive risk score which could accurately predict positive GPC-3 HCC, which may help identify potential responders for GPC-3-targeted immunotherapy.
作为 Wnt 和 HGF 信号的核心受体，聚糖蛋白-3（GPC-3）促进肿瘤的进展，并与肝细胞癌（HCC）的预后不良相关。GPC-3 已成为各种免疫疗法的靶分子，包括嵌合抗原受体 T 细胞。然而，其评估仍然依赖于有创的组织病理学检查。因此，我们旨在开发一种易于使用且非侵入性的风险评分，该评分结合术前钆塞酸增强磁共振成像（EOB-MRI）和临床指标，以预测 HCC 中 GPC-3 的阳性表达。
回顾性纳入 2016 年 1 月至 2021 年 11 月期间接受手术证实的单发 HCC 且术前接受 EOB-MRI 的连续患者。两名盲法腹部放射科医生独立评估 EOB-MRI 特征，两名肝脏病理学家确定 GPC-3 的表达。在训练数据集上，通过逻辑回归分析对病理进行预测评分系统。通过计算接收器操作特征曲线（AUC）下的面积来描述模型性能。
共纳入 278 例单发 HCC 患者（训练集，n=156；内部验证集，n=39；外部验证集，n=83）（208 例[75%] GPC-3 阳性表达）。血清甲胎蛋白>10ng/ml（AFP，优势比[OR]=2.3，4 分）和 EOB-MRI 五种特征，包括肿瘤大小>3.0cm（OR=0.5，-3 分）、非外周“洗脱”（OR=3.0，5 分）、浸润性外观（OR=9.3，10 分）、明显弥散受限（OR=3.3，5 分）和实质肿块铁保留（OR=0.2，-7 分）与 GPC-3 阳性表达显著相关。预测 GPC-3 阳性表达的评分系统的最佳阈值为 5.5 分，内部和外部验证集的 AUC 分别为 0.726 和 0.681。
基于血清 AFP 和 EOB-MRI 的五种特征，我们开发了一种易于使用且非侵入性的风险评分，可以准确预测 GPC-3 阳性 HCC，这可能有助于识别 GPC-3 靶向免疫治疗的潜在应答者。
