The journal of medical investigation : JMI · 2025
The combination of CD8 and TIM3 expression predicts survival outcomes in hepatocellular carcinoma.
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Noma Takayuki, Wada Yuma, Nishi Masaaki, Teraoku Hiroki, Yamada Shinichiro, Saito Yu, Ikemoto Tetsuya, Morine Yuji, Shimada Mitsuo
Аннотация
BACKGROUND: Tumor-infiltrating CD8+ T cells express many immune checkpoint proteins and are currently the focus of therapeutic targeting, although dramatic results have not yet been achieved in hepatocellular carcinoma (HCC). In this study, we performed a statistical analysis of immune checkpoint proteins and prognosis in HCC to evaluate its utility as a biomarker for predicting prognosis.
METHODS: We analyzed 474 HCC patients with two comprehensive miRNA profiling datasets (GSE76427:n=115 and TCGA:n=359) with clinical and transcriptomic data to examine associations between mRNA levels of CD8, TIM3, and PD-1/PD-L1. Each gene was divided into low- and high-expression groups using the tertiles of RNA expression.
RESULTS: CD8 and TIM3 expression were associated with overall survival (OS) (P=0.021 and P=0.025, respectively), while PD-1/PD-L1 levels were not associated with OS (P=0.306 and P=0.318, respectively) in TCGA dataset. Among patients with high CD8 expression, low TIM3 expression was associated with better OS (TCGA:P=0.009, Whole patient cohort (TCGA+GSE dataset):P=0.008).
CONCLUSIONS: The combination of CD8 and TIM3 expression which indicates T cell exhaustion was useful biomarker for predicting HCC prognosis than PD-1/PD-L1, suggesting that TIM3 may be a future target for immune checkpoint inhibition. J. Med. Invest. 72 : 354-360, August, 2025.
METHODS: We analyzed 474 HCC patients with two comprehensive miRNA profiling datasets (GSE76427:n=115 and TCGA:n=359) with clinical and transcriptomic data to examine associations between mRNA levels of CD8, TIM3, and PD-1/PD-L1. Each gene was divided into low- and high-expression groups using the tertiles of RNA expression.
RESULTS: CD8 and TIM3 expression were associated with overall survival (OS) (P=0.021 and P=0.025, respectively), while PD-1/PD-L1 levels were not associated with OS (P=0.306 and P=0.318, respectively) in TCGA dataset. Among patients with high CD8 expression, low TIM3 expression was associated with better OS (TCGA:P=0.009, Whole patient cohort (TCGA+GSE dataset):P=0.008).
CONCLUSIONS: The combination of CD8 and TIM3 expression which indicates T cell exhaustion was useful biomarker for predicting HCC prognosis than PD-1/PD-L1, suggesting that TIM3 may be a future target for immune checkpoint inhibition. J. Med. Invest. 72 : 354-360, August, 2025.