Expression and Prognostic Value of DNA Sensors in Hepatocellular Carcinoma.

DNA sensor proteins play an important role in transducing DNA signals to induce immune responses that initiate inflammation or clear pathogens. It has been previously shown that several DNA sensors are involved in regulating tumor biology and/or cancer immunology. However, a systemic analysis of DNA sensor expression and its correlation with prognosis has not been conducted. Here, we analyzed mRNA expression and protein abundance in liver cancer databases and found that the genes of five DNA sensors (POLR3A, PRKDC, DHX9, cGAS, and MRE11) were consistently upregulated in tumor tissue. Moreover, the expression of these DNA sensor genes correlated with patient survival. Using a gene alterations analysis, we discovered that patients with genetically altered DNA sensors had significantly lower survival compared to an unaltered group. Furthermore, receiver operator characteristic (ROC) curves confirmed that the signatures of the five DNA sensors were independent prognostic factors in hepatocellular carcinoma (HCC). Tumor-infiltrating immune cell analysis revealed that expression of all five DNA sensors correlated with the amount of B cells, CD8 T cells, CD4 T cells, Tregs, DCs, Mϕs, and neutrophils. Surprisingly, four of the DNA sensors (POLR3A, PRKDC, DHX9, and MRE11) were inversely correlated with the amount of γδ T cells. GSEA analysis showed that all five DNA sensor genes were enriched for oxidative phosphorylation and xenobiotic metabolism. These results suggest that expression of these DNA sensors is associated with a unique immune profile and metabolic regulation in HCC.