Distinct Roles of Adenosine Deaminase Isoenzymes ADA1 and ADA2: A Pan-Cancer Analysis

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. Human Protein Atlas (HPA) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were used to analyze t...

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Published in:Frontiers in immunology 2022-05, Vol.13, p.903461
Main Authors: Gao, Zhao-Wei, Yang, Lan, Liu, Chong, Wang, Xi, Guo, Wen-Tao, Zhang, Hui-Zhong, Dong, Ke
Format: Article
Language:English
Subjects:
ADA1
ADA2
Adenocarcinoma
Adenocarcinoma of Lung
Adenosine Deaminase - genetics
cancer
Carcinoma, Renal Cell
Esophageal Neoplasms
Esophageal Squamous Cell Carcinoma
Head and Neck Neoplasms
Humans
immune infiltration
Immunology
Isoenzymes
Kidney Neoplasms
Lung Neoplasms
Melanoma
Melanoma, Cutaneous Malignant
Pancreatic Neoplasms
prognosis
Skin Neoplasms
Squamous Cell Carcinoma of Head and Neck
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Summary: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. 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. 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-r
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2022.903461