The MRI histogram enhanced by disodium gadosenate can effectively predict the expression of Ki-67 in hepatocellular carcinoma before operation
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摘要:
目的 探讨钆塞酸二钠增强MRI列线图在术前预测肝细胞癌Ki-67表达状态的应用价值。 方法 回顾性分析本院2022年1月~2024年5月经病理诊断的122例肝细胞癌患者的资料，根据术后免疫组化细胞增殖水平(Ki-67指数)将患者分为Ki-67高表达组(n=71)和Ki-67低表达组(n=51)，并按7：3比例随机分为训练集(n=85)和验证集(n=37)，分析两组患者影像学参数[肿瘤直径、边缘、假包膜、瘤体区表观弥散系数(ADC)、肝胆期信号强度与正常肝实质信号强度比(SIR)、瘤周低信号]、AFP浓度及肿瘤分化程度差异，纳入LASSO回归模型筛选出最具价值的参数，并行多因素Logistic回归分析建立预测模型构建列线图，通过ROC曲线、校准曲线和决策曲线评估模型效能。 结果 训练集及验证集Ki-67高表达组甲胎蛋白≥20 ng/mL、肿瘤边缘不光滑、瘤周低信号高于Ki-67低表达组，ADC值和SIR低于Ki-67低表达组，差异有统计学意义(P < 0.05)，而肿瘤直径、假包膜的差异无统计学意义(P > 0.05)。应用LASSO回归筛选出3个最有价值参数(肿瘤ADC值、SIR及肿瘤分化程度)，多因素Logistic回归分析显示ADC值及SIR是Ki-67表达影响因素，基于以上参数建立列线图模型，其校准曲线与理想曲线贴合良好，其ROC曲线下面积为0.827，敏感度为81.2%，特异度为80%。 结论 钆塞酸二钠增强MRI列线图模型可在术前有效预测肝细胞癌Ki-67表达状态，从而实现肝细胞癌患者风险分层及个体化治疗。 Abstract:Objective To investigate the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI nomogram in preoperative prediction of the Ki-67 expression status in hepatocellular carcinoma (HCC). Methods A retrospective analysis was conducted on 122 HCC patients diagnosed pathologically from January 2022 to May 2024 at our hospital. Patients were divided into high Ki-67 expression (n=71) and low Ki-67 expression (n=51) groups based on postoperative immunohistochemical cell proliferation levels (Ki-67 index). The patients were then randomly allocated to a training set (n=85) and a validation set (n=37) in proportion. Differences in imaging parameters [tumor diameter, margin, pseudocapsule, apparent diffusion coefficient (ADC) of the tumor area, signal intensity ratio (SIR) of the hepatobiliary phase to normal liver parenchyma, and peritumoral hypointensity], alpha fetoprotein concentration, and tumor differentiation degree between the two groups were analyzed. The most valuable parameters were selected using LASSO regression, and a predictive model was established through multivariate logistic regression analysis. The performance of the model was evaluated using ROC curves, calibration curves, and decision curves. Results In both the training and validation sets, the high Ki-67 expression group had higher alpha fetoprotein levels (≥20 ng/mL), more irregular tumor margins, and more frequent peritumoral hypointensity compared to the low Ki-67 expression group. The ADC values and SIR were lower in the high Ki-67 expression group, with statistically significant differences (P < 0.05). However, there were no significant differences in tumor diameter and presence of pseudocapsules (P > 0.05). LASSO regression identified three most valuable parameters (tumor ADC, SIR, and tumor differentiation degree). Multivariate logistic regression analysis showed that ADC and SIR were influencing factors for Ki-67 expression. Based on these parameters, a Nomogram model was established. The calibration curve of the model fit well with the ideal curve, and the area under the ROC curve was 0.827, with a sensitivity of 81.2% and specificity of 80%. Conclusion Gd- EOB- DTPA enhanced MRI nomogram can effectively predict the Ki-67 expression status in HCC preoperatively, facilitating risk stratification and personalized treatment for HCC patients. -
图 1 HCC Ki-67高表达组(Ki-67：30%)，中分化HCC，AFP：10.77 ng/mL
Figure 1. HCC Ki-67 high expression group (Ki-67: 30%), moderately differentiated HCC, AFP: 10.77 ng/mL. Male, 49 years old, history of hepatitis B more than 20 years, right upper abdominal distending pain more than 1 month. Liver S6 mass shadow, the edge is not smooth, lipid suppression T1WI showed slightly low signal (A), T2WI showed slightly high signal (B), DWI showed slightly high signal (C), ADC value was 0.786 × 10-3 mm2/s, the enhancement was significantly enhanced in the arterial phase (D), the enhancement degree was reduced in the venous phase (E), and the signal was low in the hepatobiliary phase. The signal intensity ratio was 0.490, and peri-tumor low signal (F) was observed.
图 2 HCC低表达组(Ki-67：10%)，高分化HCC，AFP：4.04 ng/mL
Figure 2. HCC low expression group (Ki-67: 10%), highly differentiated HCC, AFP: 4.04 ng/mL. Male, 69 years old, physical examination revealed liver mass. Liver S8 mass shadow, smooth edge, lipid suppression T1WI slightly low signal (A), T2WI slightly high signal (B), DWI slightly high signal (C), ADC value of 0.945 × 10-3 mm2/s, enhanced significantly in the arterial phase (D), decreased in the venous phase, see false envelope ring enhancement (E). The signal intensity ratio was 0.989, and there was no low signal around tumor (F).
表 1 两组患者基本资料及分类变量对比
Table 1. Comparison of patients with basic information and classification variables between the two groups [n(%)]
Index Training set (n=85) Validation set (n=37) Ki-67 high expression group Ki-67 low expression group P Ki-67 high expression group Ki-67 low expression group P Gender 0.492 0.629 Male 41(83.7) 29(80.6) 18(81.8) 14(93.3) Female 8(16.3) 7(19.4) 4(18.2) 1(6.7) Age (year, Mean±SD) 54.6±12.2 58.1±12.9 0.201 57.7±8.4 60.2±9.1 0.392 Edge 0.003 0.037 Smooth 13(26.5) 21(58.3) 7(31.8) 10(66.7) Rough 36(73.5) 15(41.7) 15(68.2) 5(33.3) Pseudocapsule 0.714 0.361 Show 35(71.4) 27(75.0) 7(31.8) 7(46.7) Not shown 14(28.6) 9(25.0) 15(68.2) 8(53.5) Low peritumoral signal 0.011 0.022 Without 19(38.8) 24(66.7) 5(22.7) 9(60.0) Exist 30(61.2) 12(33.3) 17(77.3) 6(40.0) AFP (ng/mL) 0.013 0.009 < 20 18(36.7) 23(63.9) 4(18.2) 9(60.0) ≥20 31(63.3) 13(36.1) 18(81.8) 6(40.0) Differentiated degree < 0.001 0.047 Poorly differentiated 7(14.3) 4(11.1) 5(22.7) 0(0) Moderately differentiated 39(79.6) 17(47.2) 15(68.2) 10(66.7) Well differentiated 3(6.1) 15(41.7) 2(9.1) 5(33.3) AFP: Alpha fetoprotein. 
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表 2 两组资料MRI定量参数对比分析
Table 2. Comparative analysis of MRI quantitative parameters between the two groups [M(P25, P75)]
Index Training set (n=85) Validation set (n=37) Ki-67 high expression group Ki-67 low expression group Z P Ki-67 high expression group Ki-67 low expression group Z P Diameter of tumor(cm) 4.00(2.25, 6.90) 3.25(2.35, 5.33) -0.903 0.366 4.15(3.18, 10.0) 3.70(2.00, 6.80) -1.022 0.307 ADC (×10-3mm2/s) 0.801(0.743, 0.855) 0.878 (0.930, 0.935) -3.740 < 0.001 0.797(0.702, 0.858) 0.881(0.846, 0.915) -3.125 0.002 SIR 0.546(0.487, 0.623) 0.614 (0.518, 0.684) -2.450 0.014 0.537(0.482, 0.645) 0.692(0.605, 0.806) -3.186 0.001
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