对HIV相关和HIV阴性侵袭性B细胞淋巴瘤的分子与临床见解：预后定量生物标志物分析及治疗意义
Molecular and clinical insights into HIV-associated and HIV-negative aggressive B-cell lymphomas: prognostic quantitative biomarker analysis and therapeutic implications.
作者信息
Liu Liming, Wang Tianwa, Luo Jiping, Huang Jianrong, Huang Kaipeng, Chen Kun, Wang Chao, Cheng Zhiqiang
机构信息
Department of Pathology, Shenzhen Third People's Hospital (The Second Affiliated Hospital of Southern University of Science and Technology), Shenzhen, Guangdong, China.
Department of Pathology (Longhua Branch), Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, China.
出版信息
Front Oncol. 2025 May 27;15:1603801. doi: 10.3389/fonc.2025.1603801. eCollection 2025.
BACKGROUND
HIV-associated lymphomas (HALs) exhibit aggressive features and poorer prognosis compared to HIV-negative lymphomas. However, their molecular and clinicopathological characteristics remain unclear in the antiretroviral therapy (ART) era.
METHODS
We retrospectively analyzed 208 lymphoma patients (57 HALs, 151 HIV-negative lymphomas) diagnosed between July 2019 and March 2024. Quantitative immunohistochemistry evaluated expression levels of Ki67, CD10, BCL6, MUM1, BCL2, and MYC. Independent prognostic factors were identified using multivariate Cox regression analysis, and a survival prediction model was validated by receiver operating characteristic (ROC) curve analysis.
RESULTS
HALs exhibited significantly higher proliferative activity (Ki67 AOD: 0.92 vs. 0.82, P < 0.001), more advanced disease stages (Ann Arbor stage III/IV: 77.2% vs. 60.0%, P = 0.022), and increased Epstein-Barr virus (EBV) positivity (51.1% vs. 17.9%, P < 0.001). Immunophenotyping revealed a GCB-like phenotype in HALs, characterized by elevated CD10 and BCL6 expression and decreased MUM1 and BCL2 expression. Patients with HALs had significantly shorter survival (median: 32.1 vs. 46.1 months, P < 0.001). Multivariate analysis identified Ki67 AOD (hazard ratio [HR] = 3.04, 95% confidence interval [CI]: 3.85-10.85), International Prognostic Index (IPI) (HR = 9.35, 95% CI: 4.20-20.82), and ART duration (protective, HR = 0.29/year, 95% CI: 0.19-0.45) as independent prognostic factors. The survival model demonstrated strong predictive accuracy (1-year area under the curve [AUC] = 0.831).
CONCLUSIONS
HALs exhibit distinct molecular profiles-including elevated EBV infection, a GCB-like phenotype, increased Ki67 AOD, and decreased BCL2 expression-that contribute to significantly poorer survival compared to HIV-negative lymphomas. Integrating Ki67 AOD and IPI scores into prognostic models may enhance individualized prognosis and optimize treatment strategies for HAL patients.
背景
与HIV阴性淋巴瘤相比，HIV相关淋巴瘤（HAL）具有侵袭性特征且预后较差。然而，在抗逆转录病毒治疗（ART）时代，它们的分子和临床病理特征仍不清楚。
方法
我们回顾性分析了2019年7月至2024年3月期间诊断的208例淋巴瘤患者（57例HAL，151例HIV阴性淋巴瘤）。定量免疫组化评估了Ki67、CD10、BCL6、MUM1、BCL2和MYC的表达水平。使用多变量Cox回归分析确定独立预后因素，并通过受试者工作特征（ROC）曲线分析验证生存预测模型。
结果
HAL表现出显著更高的增殖活性（Ki67平均光密度：0.92对0.82，P<0.001）、更晚期的疾病阶段（Ann Arbor分期III/IV期：77.2%对60.0%，P=0.022）以及爱泼斯坦-巴尔病毒（EBV）阳性率增加（51.1%对17.9%，P<0.001）。免疫表型分析显示HAL具有生发中心B细胞样（GCB）表型，其特征为CD10和BCL6表达升高以及MUM1和BCL2表达降低。HAL患者的生存期明显较短（中位数：32.1对46.1个月，P<0.001）。多变量分析确定Ki67平均光密度（风险比[HR]=3.04，95%置信区间[CI]：3.85-10.85）、国际预后指数（IPI）（HR=9.35，95%CI：4.20-20.82）和ART持续时间（具有保护作用，HR=0.29/年，95%CI：0.19-0.45）为独立预后因素。生存模型显示出较强的预测准确性（1年曲线下面积[AUC]=0.831）。
结论
HAL表现出独特的分子特征，包括EBV感染增加、GCB样表型、Ki67平均光密度增加和BCL2表达降低，这导致其生存期比HIV阴性淋巴瘤明显更差。将Ki67平均光密度和IPI评分纳入预后模型可能会改善HAL患者的个体化预后并优化治疗策略。
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