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. 2023 Feb 2;18(3):19.
doi: 10.3892/mco.2023.2615. eCollection 2023 Mar.

Pan‑cancer analysis of the deoxyribonuclease gene family

Qingquan Bai  1   2 , Xiao He  3 , Tianhui Hu  2
Affiliations

Pan‑cancer analysis of the deoxyribonuclease gene family

Qingquan Bai et al. Mol Clin Oncol. .

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.

Keywords: deoxyribonuclease; immune infiltration subtype; overall survival; tumor microenvironment; tumor stemness score.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Expression of DNase genes. (A) Boxplot to show the distribution of DNase gene expression for all 33 cancer types. (B) Correlation plot to show the correlation of gene expression among the 6 DNase family members for all 33 cancer types. (C) Heatmap to show the difference of DNase gene expression comparing primary tumor to adjacent normal tissues for 18 cancer types have more than 5 adjacent normal samples. BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; STAD, stomach adenocarcinoma; THCA, thyroid carcinoma; UCEC, uterine corpus endometrial carcinoma.
Figure 2
Figure 2
Expression levels of DNase genes in primary tumor and their adjacent normal tissue for 18 cancer types with more than 5 adjacent normal samples. (A) DNASE1, (B) DNAE1L1, (C) DNASE1L2, (D) DNASE1L3, (E) DNASE2, (F) DNASE2B. Unpaired Student's t-test. *P<0.05, **P<0.01, ***P<0.001. BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; STAD, stomach adenocarcinoma; THCA, thyroid carcinoma; UCEC, uterine corpus endometrial carcinoma.
Figure 3
Figure 3
The relationship between the expression of DNase genes and the overall survival rate of 33 kinds of cancer patients by Univariate Cox expression analysis. ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, somach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Figure 4
Figure 4
DNase genes expression with immune infiltration types and the tumor microenvironment in 33 kinds of cancer. (A) The relationship between the expression of DNase genes and the immune infiltrate subtypes was tested with one-way ANOVA. ***P<0.001. (B) The relationship between the expression of DNase genes and the Stromalscore. (C) The relationship between the expression of DNase genes and the Immunescore. (D) The relationship between the expression of DNase genes and the Estimatescore. (E) The relationship between the expression of DNase genes and the Tumorpurity. C1, wound healing; C2, INF-r dominant; C3, inflammatory; C4, lymphocyte depleted; C5, immunologically quiet; C6, TGF-β dominant; ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, somach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Figure 5
Figure 5
DNase genes expression with tumor stemness and drug sensitivity. (A) The relationship between the expression of DNase genes and RNAss. (B) The relationship between the expression of DNase genes and DNAss. (C) The relationship between the expression of DNase genes and drug sensitivity. ACC, adrenocortical carcinoma; BLCA, bladder urothelial carcinoma; BRCA, breast invasive carcinoma; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; COAD, colon adenocarcinoma; DLBC, lymphoid neoplasm diffuse large B-cell lymphoma; ESCA, esophageal carcinoma; GBM, glioblastoma multiforme; HNSC, head and neck squamous cell carcinoma; KICH, kidney chromophobe; KIRC, kidney renal clear cell carcinoma; KIRP, kidney renal papillary cell carcinoma; LAML, acute myeloid leukemia; LGG, brain lower grade glioma; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MESO, mesothelioma; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PCPG, pheochromocytoma and paraganglioma; PRAD, prostate adenocarcinoma; READ, rectum adenocarcinoma; SARC, sarcoma; SKCM, skin cutaneous melanoma; STAD, somach adenocarcinoma; TGCT, testicular germ cell tumors; THCA, thyroid carcinoma; THYM, thymoma; UCEC, uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma; UVM, uveal melanoma.
Figure 6
Figure 6
DNase gene expression in HCC. (A) The relationship between the expression of DNase genes and the clinical stage tested with ANOVA in HCC. The expression of DNASE1, DNASE1L3 and DNASE2B was associated with the stage of HCC. *P<0.05, **P<0.01, ***P<0.001. (B) The relationship between the expression of DNase genes and the immune infiltrate subtypes tested with ANOVA in HCC. A significant correlation was detected between DNASE1, DNASE1L3, DNASE2 and DNASE2B expression and immune subtype. (C) The relationship between DNase gene expression and RNAss, DNAss, stromal score, immune score, and Estimate Score in HCC. C1, wound healing; C2, INF-r dominant; C3, inflammatory; C4, lymphocyte depleted; C5, immunologically quiet; C6, TGF-β dominant; RNAss, RNA stemness score; DNAss, DNA stemness score.
Figure 7
Figure 7
DNASE1L3 gene expression in HCC. (A) Expression levels of DNASE1L3 in 24 pairs of HCC samples and adjacent normal liver samples in GSE22405. (B) Expression levels of DNASE1L3 in 18 pairs of HCC samples and adjacent normal liver samples in GSE60502. (C) Expression levels of DNASE1L3 in 60 pairs of HCC samples and adjacent normal liver sample in GSE64041. (D) IHC staining of 75 pairs of HCC and adjacent normal liver. (E) DNASE1L3 protein staining in HCC. (F) DNASE1L3 protein staining in healthy liver tissue. **P<0.01, ***P<0.001 (paired Student's t-test). HCC, hepatocellular carcinoma.
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