Expression Patterns of HOX Gene Family Defines Tumor Microenvironment and Immunotherapy in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) pathophysiology is prevalently related with HOX genes. However, the study on associations of extensive HOX genes with tumor microenvironment and drug sensitivity of HCC remains scarce. The data sets of HCC were downloaded from TCGA, ICGC, and GEO by bioinformatics method and analyzed. Based on a computational frame, HCC samples were divided into a high and a low HOXscore group, and significantly shorter survival time in the high HOXscore was observed relative to low HOXscore group using survival analysis. Gene set enrichment analysis (GSEA) revealed that the high HOXscore group was more likely to be enriched in cancer-specific pathways. Furthermore, the high HOXscore group was involved in the infiltration of inhibitory immune cells. In response to anti-cancer drugs, the high HOXscore group was more sensitive to mitomycin and cisplatin. Importantly, the HOXscore was associated with the therapeutic efficacy of PD-L1 blockade, suggesting that the development of potential drugs targeting these HOX genes to aid the clinical benefits of immunotherapy is needed. In addition, RT-qPCR and immunohistochemistry showed 10 HOX genes mRNA expression was higher in HCC compared to the normal tissues. This study provides a comprehensive analysis of HOX genes family in HCC and revealed the potential function of these HOX genes family in tumor microenvironment (TME) and identified their therapeutic liability in targeted therapy and immunotherapy. Eventually, this work highlights the cross-talk and potential clinical utility of HOX genes family in HCC therapy.