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

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

doi:10.3389/fonc.2024.1456748

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

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

Authors

Zhishen Tang^#^{1

2}, Wei Wang^#^{1

2}, Bo Gao^#³, Xuyang Liu², Xiangyu Liu^{1

2}, Yingquan Zhuo², Jun Du², Fujun Ai⁴, Xianwu Yang², Huajian Gu¹

Affiliations

¹ Department of Pediatric Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
² School of Clinical Medicine, Guizhou Medical University, Guiyang, China.
³ Department of Radiology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
⁴ Department of Pathology and Pathophysiology, Guizhou Medical University, Guiyang, China.

^# Contributed equally.

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.

Keywords: Tim-3 expression; bioanalysis; habitat radiomics; hepatocellular carcinoma; immunotherapy.