Distinct Roles of Adenosine Deaminase Isoenzymes ADA1 and ADA2: A Pan-Cancer Analysis
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Published on: July 20, 2016
Zhao-Wei Gao1, Lan Yang1, Chong Liu1
1Department of Clinical Laboratory, Tangdu Hospital, Air Force Medical University, Xi'an, China.
Objective:
Adenosine deaminase (ADA) plays an important role in immune response, which includes two isoenzymes: ADA1 and ADA2. This study aims to explore the roles of ADA1 and ADA2 in cancers.
Methods:
Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were used to analyze the mRNA expression of ADA1 and ADA2 in human normal cells and tumor tissues. The enzyme assay was used to detect the ADA1 and ADA2 activities in serum from cancer patients. The Kaplan-Meier (KM) plotter was used to analyze the prognostic value of ADA1 and ADA2. TIMER2.0 was used to explore how ADA1 and ADA2 correlate with immune infiltration and immune checkpoints. cBioPortal database was used to investigate the mutations of ADA1 and ADA2. LinkedOmics was used to screen the ADA1 and ADA2 expression-related genes.
Results:
ADA1 was significantly increased in several tumor tissues, including cholangiocarcinoma (CHOL), lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), head and neck squamous cell carcinoma (HNSC), kidney renal clear cell carcinoma (KIRC), ovarian serous cystadenocarcinoma (OV), pancreatic adenocarcinoma (PAAD), thymoma (THYM), and uterine carcinosarcoma (UCS). ADA2 expression was significantly increased in esophageal carcinoma (ESCA), glioblastoma multiforme (GBM), acute myeloid leukemia (LAML), OV, PAAD, skin cutaneous melanoma (SKCM), and stomach adenocarcinoma (STAD). There were no significant changes in serum ADA1 activities in most cancers, while serum ADA2 activities were increased in most cancers. For prognosis, high ADA1 expression was associated with the poor survival in several cancers, including esophageal squamous cell carcinoma (ESCC), HNSC, KIRC, kidney renal papillary cell carcinoma (KIRP), liver hepatocellular carcinoma (LIHC), lung adenocarcinoma (LUAD), and uterine corpus endometrial carcinoma (UCEC). However, high ADA2 expression showed a favorable prognosis in breast invasive carcinoma (BRCA), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), HNSC, KIRC, KIRP, LUAD, OV, PAAD, sarcoma, and THYM. ADA1 showed a moderate positive correlation with multiple infiltrating immune cells in most cancers. ADA2 was positively correlated with B cells, CD8 T cells, monocytes/macrophages, and dendritic cells (DCs) and was strongly negatively correlated with myeloid-derived suppressor cells. Function analysis showed that ADA1 expression-related genes were mainly enriched in cell division biological progression. However, ADA2-related genes were mainly associated with immune response.
Conclusion:
As isoenzymes, ADA1 and ADA2 showed opposite prognostic values and different correlative patterns with immune infiltrating. These data demonstrated the distinct roles of ADA1 and ADA2 in cancer. ADA2 might act as a protective factor in cancer.
Insights
Adenosine deaminase isoenzymes ADA1 and ADA2 show distinct roles in cancer. ADA1 correlates with poor prognosis and cell division, while ADA2 is linked to favorable outcomes and immune response, potentially acting as a protective factor.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Adenosine deaminase (ADA) is crucial for immune response, existing as two isoenzymes: ADA1 and ADA2.
- Understanding the specific roles of ADA1 and ADA2 in various cancers is essential for developing targeted therapies.
Purpose of the Study:
- To investigate the differential roles of ADA1 and ADA2 in cancer development, prognosis, and immune infiltration.
- To analyze the expression patterns, prognostic values, and immune correlations of ADA1 and ADA2 across multiple cancer types.
Main Methods:
- Utilized Human Protein Atlas (HPA) and GEPIA2 for mRNA expression analysis.
- Employed enzyme assays for serum ADA activity, Kaplan-Meier plotter for prognostic analysis, and TIMER2.0 for immune infiltration correlation.
- Investigated mutations via cBioPortal and expression-related genes using LinkedOmics.
Main Results:
- ADA1 mRNA was elevated in several cancers (e.g., HNSC, KIRC, PAAD), associated with poor survival and enriched cell division pathways.
- ADA2 mRNA was upregulated in other cancers (e.g., ESCA, GBM, STAD), linked to favorable prognosis and immune response pathways.
- Serum ADA2 activity increased in most cancers, contrasting with minimal changes in ADA1 activity; ADA2 correlated positively with immune cells and negatively with suppressive cells.
Conclusions:
- ADA1 and ADA2 exhibit opposing prognostic values and distinct immune infiltration correlations in cancer.
- These findings highlight the unique functions of ADA1 and ADA2 in oncogenesis.
- ADA2 may function as a protective factor in the cancer landscape.
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