Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Front Immunol. 2024 Apr 11;15:1358306. doi: 10.3389/fimmu.2024.1358306. eCollection 2024.
Targeted and Immunotherapy has emerged as a new first-line treatment for advanced hepatocellular carcinoma (aHCC). To identify the appropriate targeted and immunotherapy, we implemented next generation sequencing (NGS) to provide predictive and prognostic values for aHCC patients.
Pretreatment samples from 127 HCC patients were examined for genomic changes using 680-gene NGS, and PD-L1 expression was detected by immunohistochemistry. Demographic and treatment data were included for analyses of links among treatment outcomes, drug responses, and genetic profiles. A prognostic index model for predicting benefit from treatment was constructed, taking into account of biomarkers, including , , PD-L1, and tumor mutation burden (TMB) as possible independent prognostic factors.
The multivariate Cox regression analyses showed that PD-L1≥1% (HR 25.07, 95%CI 1.56 - 403.29, p=0.023), TMB≥5Mb (HR 86.67, 95% CI 4.00 - 1876.48, p=0.004), TERT MU (HR 84.09, 95% CI 5.23 - 1352.70, p=0.002) and TP53 WT (HR 0.01, 95%CI 0.00 - 0.47, p=0.022) were independent risk factors for overall survival (OS), even after adjusting for various confounders. A prognostic nomogram for OS was developed, with an area under the ROC curve of 0.91, 0.85, and 0.98 at 1-, 2-, and 3- year, respectively, and a prognostic index cutoff of 1.2. According to the cutoff value, the patients were divided into the high-risk group (n=29) and low-risk group (n=98). The benefit of targeted and immunotherapy in the low-risk group was not distinguishable according to types of agents. However, treatment of Atezolizumab and Bevacizumab appeared to provide longer OS in the high-risk group (12 months vs 9.2, 9, or 5 months for other treatments, p<0.001).
The prognostic model constructed by PD-L1, TMB, , and can identify aHCC patients who would benefit from targeted and immunotherapy, providing insights for the personalized treatment of HCC.
针对和免疫疗法已成为晚期肝细胞癌（aHCC）的新一线治疗方法。为了确定合适的靶向和免疫治疗方法，我们使用下一代测序（NGS）为 aHCC 患者提供预测和预后价值。
对 127 例 HCC 患者的预处理样本进行 680 基因 NGS 检测，并通过免疫组织化学检测 PD-L1 表达。纳入人口统计学和治疗数据，分析治疗结果、药物反应和遗传特征之间的联系。构建了一个预测治疗获益的预后指数模型，考虑了生物标志物，包括 PD-L1、TMB 和肿瘤突变负荷（TMB）作为可能的独立预后因素。
多变量 Cox 回归分析显示，PD-L1≥1%（HR 25.07，95%CI 1.56-403.29，p=0.023）、TMB≥5Mb（HR 86.67，95%CI 4.00-1876.48，p=0.004）、TERT MU（HR 84.09，95%CI 5.23-1352.70，p=0.002）和 TP53 WT（HR 0.01，95%CI 0.00-0.47，p=0.022）是总生存期（OS）的独立危险因素，即使在调整了各种混杂因素后也是如此。建立了 OS 的预后列线图，ROC 曲线下面积分别为 0.91、0.85 和 0.98，在 1、2 和 3 年时的截断值为 1.2。根据截断值，患者分为高危组（n=29）和低危组（n=98）。低危组的各种靶向和免疫治疗药物的疗效没有明显差异。然而，阿特珠单抗和贝伐单抗治疗似乎为高危组提供了更长的 OS（12 个月 vs 9.2、9 或 5 个月的其他治疗，p<0.001）。
由 PD-L1、TMB、和 构建的预后模型可以识别出从靶向和免疫治疗中获益的 aHCC 患者，为 HCC 的个体化治疗提供了思路。
Zotero 插件
