Pan‑cancer analysis of the deoxyribonuclease gene family.

Abstract

Deoxyribonuclease (DNase) is an enzyme that catalyzes the cleavage of phosphodiester bonds in the main chain of DNA to degrade DNA. DNase serves a vital role in several immune-related diseases. The present study linked the expression of DNase with overall survival (OS), performed pan-cancer co-expression analysis, and assessed the association between DNase and immune infiltration subtypes, tumor microenvironment and drug sensitivity through pan-cancer studies. Furthermore, gene expression data and clinical data were downloaded from The Cancer Genome Atlas. Next, through a series of bioinformatics analyses, DNase expression and survival, immune subtypes, tumor microenvironment and drug sensitivity in 33 tumor types were systematically studied. The expression of the DNase gene family was shown to have an apparent intratumoral heterogeneity. The expression of DNase 2, lysosomal (DNASE2) was the highest in tumors, whereas that of DNASE2 β was the lowest. DNase 1-like 3 (DNASE1L3) was mainly downregulated in tumors, whereas the rest of the DNases were mainly upregulated in tumors. The expression of DNase family members was also found to be associated with the OS rate of patients. DNase family genes may serve an essential role in the tumor microenvironment. DNase family gene expression was related to the content of cytotoxic cells, Immunescore, Stromalscore, Estimatescore and Tumorpurity. The present study also revealed that the DNase genes may be involved in the drug resistance of cancer cells. Finally, the correlation between DNase, and clinical stage and tumor microenvironment in hepatocellular carcinoma (HCC) was studied. In addition, the difference in DNASE1L3 expression between HCC and adjacent normal tissues, and the relationship between DNASE1L3 expression and clinical stage was verified by analyzing three groups in a Gene Expression Omnibus dataset and by performing immunohistochemistry. In conclusion, the present study assessed DNase gene expression, analyzed its relationship with patient OS, performed pan-cancer co-expression analysis, and assessed the association between DNase and immune infiltration subtypes, tumor microenvironment and drug sensitivity. The present study also confirmed the value of further laboratory research on DNases and their prospects in clinical cancer treatment.