Development and Validation of TACE Refractoriness-Related Diagnostic and Prognostic Scores and Characterization of Tumor Microenvironment Infiltration in Hepatocellular Carcinoma

BackgroundTranscatheter arterial chemoembolization LIHC, Liver hepatocellular carcinoma; (TACE) is a valid therapeutic method for hepatocellular carcinoma (HCC). However, many patients respond poorly to TACE, thus leading to an adverse outcome. Therefore, finding new biomarkers for forecasting TACE refractoriness occurrence and prognosis becomes one of the current research priorities in the field of HCC treatment. Materials and MethodsBased on microarray datasets and a high-throughput sequencing dataset, the TACE refractoriness-related genes (TRGs) were identified by differential expression analysis. LASSO and Cox regression were applied to construct TACE refractoriness diagnostic score (TRD score) and prognostic score (TRP score) and validated their accuracy in external datasets. Functional correlation of TRP score was analyzed by gene set variation analysis and Gene Ontology. CIBERSORT and IMMUNCELL AI algorithms were performed to understand the correlation between the two scores and immune activity. We further carried out the efficacy analysis of immunotherapy and targeted drugs in the different TRP score groups. Furthermore, a nomogram was built by integrating various independent prognostic factors and validated its effectiveness in different datasets. ResultsWe identified 487 TRGs combined with GSE104580 and TCGA datasets. Then four novel TRGs (TTK, EPO, SLC7A11, and PON1) were screened out to construct TRD score and TRP score models, and both two scores had good predictive ability in external datasets. Tumors with high TRP score show an immunosuppressive phenotype with more infiltrations of regulatory T cells and macrophages. Immunotherapy and chemotherapy response evaluation revealed patients with a high TRP score demonstrated well reactions to immune checkpoint inhibitors (ICIs) and sorafenib. TRP score, TNM stage, and cancer type were brought into the combined nomogram with optimum prediction. ConclusionsOur research provided dependable and simplified methods for patients with HCC to assess tumors' susceptibility to TACE refractoriness and prognosis and guide patients' clinical therapy choices.

Automated summary

This study aims to identify new biomarkers for predicting the occurrence and prognosis of TACE refractoriness in hepatocellular carcinoma (HCC). By analyzing microarray datasets and a high-throughput sequencing dataset, several genes related to TACE refractoriness were identified. Diagnostic and prognostic scores were constructed and validated using external datasets. The correlation between these scores and immune activity was also examined. The study further analyzed the efficacy of immunotherapy and targeted drugs in different score groups and built a nomogram for predicting prognosis. The findings provide methods for assessing susceptibility to TACE refractoriness and guiding clinical therapy choices in HCC patients.