Identification of a Interferon-Stimulated gene Signature for Predicting Prognosis, Tumor Microenvironment, and Drug Candidates in Hepatocellular Carcinoma

Background: Interferon-stimulated genes (ISGs) play critical roles not only in antiviral defense and adaptive immunity but also in the progression of cancer and the immune response. However, there is limited research delineating the relationship between ISGs and HCC prognosis, tumor microenvironment (TME), and response to immunotherapy. Methods The transcriptional and relevant clinical data of HCC were downloaded from The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) databases, which were used for internal and external validation, respectively. First, ISGs that were differentially expressed in HCC tissues compared to adjacent non-tumor tissues and were also associated with prognosis were screened. Second, the prognostic model based on ISGs was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis. Next, we analyzed the relationship between the prognosis model and clinical outcomes, clinical and pathological features, immune microenvironment, and response to immunotherapy. Finally, the expression levels of three ISGs were validated by real-time PCR in normal and HCC cell lines. Results Three ISGs (BUB1, NDC80, and SOCS2) were selected to establish the prognostic model. The model has good predictive power for clinical outcomes, clinical and pathological features, gene mutations, tumor microenvironment, and response to immunotherapy. The ROC curve analysis confirmed the predictive efficacy of the model. Furthermore, the results of real-time PCR showed that BUB1 and NDC80 were highly expressed in tumor cell lines, and SOCS2 was highly expressed in normal liver cell lines. Conclusion The prognostic model based on three ISGs can accurately predict the clinical outcomes, clinical and pathological features, gene mutations, tumor microenvironment, and response to immunotherapy in HCC patients.