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通过腹部增强CT影像组学揭示肝细胞癌中Tim-3免疫检查点的表达

Unveiling Tim-3 immune checkpoint expression in hepatocellular carcinoma through abdominal contrast-enhanced CT habitat radiomics.

作者信息

Tang Zhishen, Wang Wei, Gao Bo, Liu Xuyang, Liu Xiangyu, Zhuo Yingquan, Du Jun, Ai Fujun, Yang Xianwu, Gu Huajian

机构信息

Department of Pediatric Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China.

School of Clinical Medicine, Guizhou Medical University, Guiyang, China.

出版信息

Front Oncol. 2024 Nov 8;14:1456748. doi: 10.3389/fonc.2024.1456748. eCollection 2024.

Abstract

INTRODUCTION

Immune checkpoint inhibitors (ICIs) are important systemic therapeutic agents for hepatocellular carcinoma (HCC), among which T-cell immunoglobulin and mucin-domain containing protein 3 (Tim-3) is considered an emerging target for ICI therapy. This study aims to evaluate the prognostic value of Tim-3 expression and develop a predictive model for Tim-3 infiltration in HCC.

METHODS

We collected data from 424 HCC patients in The Cancer Genome Atlas (TCGA) and data from 102 pathologically confirmed HCC patients from our center for prognostic analysis. Multivariate Cox regression analyses were performed on both datasets to determine the prognostic significance of Tim-3 expression. In radiomics analysis, we used the K-means algorithm to cluster regions of interest in arterial phase enhancement and venous phase enhancement images from patients at our center. Radiomic features were extracted from three subregions as well as the entire tumor using pyradiomics. Five machine learning methods were employed to construct Habitat models based on habitat features and Rad models based on traditional radiomic features. The predictive performance of the models was compared using ROC curves, DCA curves, and calibration curves.

RESULTS

Multivariate Cox analyses from both our center and the TCGA database indicated that high Tim-3 expression is an independent risk factor for poor prognosis in HCC patients. Higher levels of Tim-3 expression were significantly associated with worse prognosis. Among the ten models evaluated, the Habitat model constructed using the LightGBM algorithm showed the best performance in predicting Tim-3 expression status (training set vs. test set AUC 0.866 vs. 0.824).

DISCUSSION

This study confirmed the importance of Tim-3 as a prognostic marker in HCC. The habitat radiomics model we developed effectively predicted intratumoral Tim-3 infiltration, providing valuable insights for the evaluation of ICI therapy in HCC patients.

摘要

引言

免疫检查点抑制剂(ICI)是肝细胞癌(HCC)重要的全身治疗药物,其中含T细胞免疫球蛋白和粘蛋白结构域蛋白3(Tim-3)被认为是ICI治疗的一个新兴靶点。本研究旨在评估Tim-3表达的预后价值,并建立一个预测HCC中Tim-3浸润的模型。

方法

我们收集了癌症基因组图谱(TCGA)中424例HCC患者的数据以及来自我们中心102例经病理证实的HCC患者的数据进行预后分析。对两个数据集均进行多因素Cox回归分析,以确定Tim-3表达的预后意义。在放射组学分析中,我们使用K均值算法对来自我们中心患者的动脉期增强和静脉期增强图像中的感兴趣区域进行聚类。使用pyradiomics从三个子区域以及整个肿瘤中提取放射组学特征。采用五种机器学习方法构建基于栖息地特征的Habitat模型和基于传统放射组学特征的Rad模型。使用ROC曲线、DCA曲线和校准曲线比较模型的预测性能。

结果

来自我们中心和TCGA数据库的多因素Cox分析表明,高Tim-3表达是HCC患者预后不良的独立危险因素。Tim-3表达水平越高,预后越差。在所评估的十个模型中,使用LightGBM算法构建的Habitat模型在预测Tim-3表达状态方面表现最佳(训练集与测试集AUC分别为0.866和0.824)。

讨论

本研究证实了Tim-3作为HCC预后标志物的重要性。我们开发的栖息地放射组学模型有效地预测了肿瘤内Tim-3浸润,为评估HCC患者的ICI治疗提供了有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/88c8/11581969/8718208faaee/fonc-14-1456748-g001.jpg

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