A CD8⁺ T cell‐related genes prognostic model for hepatocellular carcinoma patients

Abstract

Immune checkpoint blockade (ICB) therapy is a promising treatment for hepatocellular carcinoma (HCC). However, it is limited by low response rates. Tumour‐infiltrating immune cells (TIICs), specifically CD8+ T cells, in the tumour microenvironment (TME) are related to tumour immune responses and are potential predictors for immunotherapeutic and survival outcomes. Therefore, we established a new CD8+ T cell‐related genes prognostic index (CD8T‐RGPI) for evaluating immune responses and prognostic outcomes for HCC. Using the TCGA databases, we evaluated the RNA‐seq data of CD8+ T cell‐related genes with gene co‐expression network. Then, the CD8T‐RGPI model was built by combining univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. The nomogram exhibited a good prediction ability for HCC patients' prognosis in either TCGA or ICGC databases. The CD8T‐RGPI was elevated in patients with high T, M and TNM stages. Functional enrichment analyses revealed that in CD8T‐RGPI high‐risk group, tumour‐related and immunosuppressive pathways, such as focal adhesion, aerobic glycolysis, HIF1 transcription factor pathway, IL‐4 and IL‐13 signalling were significantly enriched. Moreover, for CD8T‐RGPI high‐risk HCC patients, immune tolerance and immunosurveillance escape was associated with poor therapeutic outcomes for ICB therapy. The CD8T‐RGPI low‐risk HCC patients with elevated immune infiltration levels were associated with good immunotherapeutic responses to ICB. Our findings provide prospective prognostic biomarkers and elucidate on HCC immunotherapy.

Hypoxia-induced LncRNA CTD-2510F5.4 facilitates hepatocellular carcinoma cell proliferation and invasion, predicts prognosis, tumor microenvironment, and drug efficacy in patients with hepatocellular carcinoma

“…Our study demonstrated that the high-CTD-2510F5.4 subgroup had higher TIDE scores and signi cantly lower ORR to ICI therapy compared to the low-CTD-2510F5.4 subgroup. The TIDE score is a reliable predictor of the response to ICI therapy(Fu et al 2020, Chang et al 2022). Furthermore, we observed that the high-CTD-2510F5.4 subgroup had higher IC50 values for sunitinib and dasatinib but lower IC50 values for cisplatin, doxorubicin, and rapamycin compared to the low-CTD-2510F5.4 subgroup.…”