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一种基于新型免疫分型的风险分层模型可预测中国肝细胞癌患者的术后预后及辅助性经动脉化疗栓塞术的获益情况。

A Novel Immunotype-based Risk Stratification Model Predicts Postoperative Prognosis and Adjuvant TACE Benefit in Chinese Patients with Hepatocellular Carcinoma.

作者信息

Li Tian-En, Zhang Ze, Wang Yi, Xu Da, Dong Jian, Zhu Ying, Wang Zheng

机构信息

Department of General Surgery, Qilu Hospital, Shandong University, Jinan 250012, China.

Department of General Surgery, Huashan Hospital & Cancer Metastasis Institute, Fudan University, Shanghai 200040, China.

出版信息

J Cancer. 2021 Mar 15;12(10):2866-2876. doi: 10.7150/jca.54408. eCollection 2021.

Abstract

: The tumor microenvironment can be divided into inflamed, immune-excluded and immunedesert phenotypes according to CD8 T cell categories with differential programmed cell death protein 1 (PD-L1) expression. The study aims to construct a novel immunotype-based risk stratification model to predict postsurgical survival and adjuvant trans-arterial chemoembolization (TACE) response in patients with hepatocellular carcinoma (HCC). A total of 220 eligible HCC patients participated in this study. CD8 T cell infiltration and PD-L1 expression mode were estimated by immunohistochemical staining. A risk stratification model was developed and virtualized by a nomogram that integrated these independent prognostic factors. The postoperative prognosis and adjuvant TACE benefits were evaluated with a novel immunotype-based risk stratification model. A total of 220 patients were finally identified. Immune-desert, immune-excluded, and inflamed immunotypes represented 45%, 24%, and 31% of HCC, respectively. Univariate and multivariate analyses identified immunotype and PD-L1 expression mode as independent prognostic factors for overall survival time (OS) and recurrence-free survival time (RFS). The nomogram was constructed by integrating immunotype, PD-L1 expression, Barcelona Clinic Liver Cancer (BCLC) stage and tumor grade. The C-index was 0.794 in the training cohort and 0.813 in the validation cohort. A risk stratification system was constructed based on the nomogram classifying HCC patients into 3 risk groups. The average OS times in the low-risk, intermediate-risk and high-risk groups in all cohorts were 77.1 months (95% CI 71.4-82.9), 53.7 months (95% CI 48.2-59.2), and 25.6 months (95% CI 21.4-29.7), respectively. Further analysis showed that OS was significantly improved by adjuvant TACE in the low- and intermediate-risk groups (0.041 and =0.010, respectively) but not in the high-risk group (=0.398). A novel immunotype-based risk stratification model was built to predict postoperative prognosis and adjuvant TACE benefit in HCC patients. These tools can assist in building a more customized method of HCC treatment.

摘要

肿瘤微环境可根据程序性细胞死亡蛋白1(PD-L1)表达不同的CD8 T细胞类别分为炎症型、免疫排除型和免疫沙漠型表型。本研究旨在构建一种基于新型免疫分型的风险分层模型,以预测肝细胞癌(HCC)患者术后生存率及辅助性经动脉化疗栓塞术(TACE)疗效。共有220例符合条件的HCC患者参与本研究。通过免疫组化染色评估CD8 T细胞浸润及PD-L1表达模式。通过整合这些独立预后因素的列线图建立并虚拟了风险分层模型。采用基于新型免疫分型的风险分层模型评估术后预后及辅助性TACE疗效。最终共纳入220例患者。免疫沙漠型、免疫排除型和炎症型免疫表型分别占HCC的45%、24%和31%。单因素和多因素分析确定免疫分型和PD-L1表达模式为总生存时间(OS)和无复发生存时间(RFS)的独立预后因素。通过整合免疫分型、PD-L1表达、巴塞罗那临床肝癌(BCLC)分期和肿瘤分级构建列线图。训练队列的C指数为0.794,验证队列的C指数为0.813。基于列线图构建了一个风险分层系统,将HCC患者分为3个风险组。所有队列中低风险、中风险和高风险组的平均OS时间分别为77.1个月(95%CI 71.4 - 82.9)、53.7个月(95%CI 48.2 - 59.2)和25.6个月(95%CI 21.4 - 29.7)。进一步分析表明,辅助性TACE可使低风险和中风险组的OS显著改善(分别为0.041和 =0.010),但高风险组未改善(=0.398)。构建了一种基于新型免疫分型的风险分层模型,以预测HCC患者术后预后及辅助性TACE疗效。这些工具有助于建立更个性化的HCC治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d441/8040877/b9a1425982a9/jcav12p2866g001.jpg

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