Study on gene signatureabel score for predicting prognosis based on TACE response genes in hepatocellular carcinoma

Abstract

Abstract: Objective: Predicting the response to transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) is a clinical necessity. This study developed a prognostic gene signature score based on TACE-responsive genes to predict TACE response and prognosis.
Methods: In the GSE104580 dataset, differential expression analysis and weighted gene co‐expression network analysis (WGCNA) were used to identify TACE-responsive genes. In the GSE14520 dataset, Least Absolute Shrinkage Selection Operator (LASSO) - Cox regression model was used to analyze prognosis-related response genes and construct gene signature scores, and then validated in the The Cancer Genome Atlas database and the Human Protein Atlas. The CIBERSORT algorithm was used to analyze the abundance of immune infiltration between TACE responders and non-responders; meanwhile, the relationship with the gene expression of 36 immune checkpoints was analyzed. The CIBERSORT algorithm was used to analyze the immune infiltration of TACE response and non-response; meanwhile, the relationship with the gene expression of 36 immune checkpoints was analyzed.
Results: A total of 276 differentially expressed genes were identified in the GSE104580 dataset (all adj.P<0.05); in WGCNA, module 7 (number of genes = 846) and module 8 (number of genes = 127) were identified to be associated with TACE responses. LASSO-Cox regression model found that CTSO, CLGN and RTP4 genes were independently correlated with patient prognosis (all P<0.05). The area under the curve (AUC) of the gene signature score for predicting 1-, 3-, and 5-years death rates was 0.812(0.748-0.965)、0.785(0.687-0.845), and 0.755(0.697-0.838), respectively. Multiple tumors, TNM stage and gene signature score were independently correlated with the prognosis of patients (all P<0.05). The AUC of Nomogram for predicting 1-, 3-, and 5-year overall survival rates were 0.729 (0.455-0.915), 0.753 (0.651-0.915), and 0.727 (0.616-0.821), respectively. There were differences in the abundance of various immune cells between TACE-responsive and no-responsive patients (P<0.05). CTSO, CLGN and RTP4 genes were correlated with the expression of various immune cells and immune checkpoints (all P<0.05).
Conclusion: Gene signature scores based on CTSO, CLGN and RTP4 genes can predict TACE response and prognosis in HCC patients. The Nomogram constructed by the combination of gene signature scores and clinicopathological parameters is helpful for the clinical translation of research results.

Key words: Hepatocellular carcinoma, Transarterial chemoembolization, Gene signature score, Nomogram, Predictive model

Yan Dong, Han Shanshan, Cao Jiawei, Xu Fei, Li Huai. Study on gene signatureabel score for predicting prognosis based on TACE response genes in hepatocellular carcinoma[J]. Electronic Journal of Liver Tumor, 2025, 12(3): 7-18.

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