基于动脉环-血管侵犯联合Ki-67/GPC-3表达的肝细胞癌预后分层模型构建

Construction of a prognostic stratification model for hepatocellular carcinoma based on arterial ring-vascular invasion combined with Ki-67/GPC-3 expression

  • 摘要:
    目的 系统评估免疫组织化学指标Ki-67、GPC-3、CD34表达与肝细胞癌患者生存期及磁共振成像(magnetic resonance imaging,MRI)影像特征的相关性,并构建整合分子标志物与影像特征的生存期预测模型。
    方法 回顾性分析2018年1月至2021年6月中国人民解放军北部战区总医院收治的肝细胞癌患者48例。采用Kaplan-Meier法及Log-rank检验比较各组生存期。采用χ2检验比较各组分类变量频率。进一步通过多变量Cox回归筛选独立预后因素,建立预后指数公式,并采用Bootstrap法验证模型效能(C-index与IDI)。
    结果  Ki-67阳性组(Ki-67指数≥30%)与阴性组平均生存期分别为(996.99±89.72)天和(1117.40±145.49)天(P<0.05),且Ki-67高表达与病灶边缘不规则、动脉环形成及血管侵犯显著相关(P<0.05)。GPC-3阳性组与阴性组平均生存期分别为(917.95±90.14)天和(1115.40±153.14)天(P<0.05),其表达与动脉环征象及血管侵犯相关(P<0.05)。CD34阳性组与阴性组平均生存期分别为(1017.55±90.15)天和(1 079.74±144.19)天,其表达与肿瘤直径>3 cm及血管侵犯相关(P<0.05),但多因素分析显示其无独立预后价值(HR=1.15,P=0.210)。基于多因素Cox回归构建预后预测模型:PI=0.615×Ki-67+0.531×GPC-3+0.336×肿瘤大小+0.470×血管侵犯,验证队列C-index=0.78(95%CI:0.70~0.86)。风险分层显示:低危组(PI≤0.8)3年生存率>65%,中危组(0.8<PI≤1.6)为30%~65%,高危组(PI>1.6)<30%(Log-rank P<0.001)。
    结论 Ki-67和GPC-3是肝细胞癌的独立预后因素,其高表达与特征性MRI征象(边缘不规则、动脉环、血管侵犯)显著相关;CD34主要反映肿瘤大小及侵袭性,但无独立预后价值。所建预测模型可实现个体化风险分层,为临床治疗决策(靶向/免疫治疗或肝移植评估)提供量化依据。

     

    Abstract:
    Objective To systematically evaluate the correlation between the expression of immunohistochemical markers (Ki-67, GPC-3, and CD34) and overall survival as well as magnetic resonance imaging (MRI) features in patients with hepatocellular carcinoma (HCC), and to construct a survival prediction model integrating molecular biomarkers and imaging characteristics.
    Methods We retrospectively analyzed 48 HCC patients admitted to the Chinese PLA General Hospital of Northern Theater Command between January 2018 and June 2021. Kaplan–Meier curves and the Log-rank test were used to compare survival between groups. The chi-square test was applied to compare categorical variables. Multivariate Cox regression was employed to identify independent prognostic factors and to establish a prognostic index formula. Model performance was validated using the Bootstrap method (C-index and IDI).
    Results The mean survival times were (996.99 ± 89.72) days for the Ki-67-positive group (Ki-67≥30%) and (1117.40 ± 145.49) days for the Ki-67-negative group (P<0.05). High Ki-67 expression was significantly associated with irregular lesion margins, arterial-ring formation, and vascular invasion (P<0.05). The mean survival times were (917.95 ± 90.14) days for the GPC-3-positive group and (1115.40 ± 153.14) days for the GPC-3-negative group (P < 0.05); GPC-3 expression correlated with the arterial-ring sign and vascular invasion (P<0.05). For CD34, mean survival was (1017.55 ± 90.15) days in the positive group and (1079.74 ± 144.19) days in the negative group. CD34 expression was associated with tumor size >3 cm and vascular invasion (P<0.05), but multivariate analysis showed no independent prognostic value (HR=1.15, P=0.210). The prognostic prediction model based on multivariate Cox regression was: PI = 0.615 × Ki-67 + 0.531 × GPC-3 + 0.336 × tumor size + 0.470 × vascular invasion. The C-index of the validation cohort was 0.78 (95% CI: 0.70–0.86). Risk stratification showed 3-year survival rates of >65% in the low-risk group (PI≤0.8), 30–65% in the intermediate-risk group (0.8<PI≤1.6), and <30% in the high-risk group (PI>1.6) (Log-rank P<0.001).
    Conclusions Ki-67 and GPC-3 are independent prognostic factors for HCC, and their high expression is significantly associated with characteristic MRI signs (irregular margins, arterial rings, and vascular invasion). CD34 mainly reflects tumor size and invasiveness but has no independent prognostic value. The developed prediction model enables individualized risk stratification and provides a quantitative basis for clinical treatment decisions (targeted/immunotherapy or liver-transplantation evaluation).

     

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