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腺苷脱氨酶同工酶 ADA1 和 ADA2 的不同作用：泛癌分析。

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

机构信息

Department of Clinical Laboratory, Tangdu Hospital, Air Force Medical University, Xi'an, China.

出版信息

Front Immunol. 2022 May 18;13:903461. doi: 10.3389/fimmu.2022.903461. eCollection 2022.

DOI:10.3389/fimmu.2022.903461
PMID:35663977
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9157497/
Abstract

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.

摘要

目的：腺苷脱氨酶（ADA）在免疫反应中发挥重要作用，包括两种同工酶：ADA1 和 ADA2。本研究旨在探讨 ADA1 和 ADA2 在癌症中的作用。

方法：使用人类蛋白质图谱（HPA）和基因表达谱交互式分析（GEPIA2）数据库分析 ADA1 和 ADA2 在人正常细胞和肿瘤组织中的 mRNA 表达。酶测定法用于检测癌症患者血清中的 ADA1 和 ADA2 活性。Kaplan-Meier（KM）绘图器用于分析 ADA1 和 ADA2 的预后价值。TIMER2.0 用于探索 ADA1 和 ADA2 与免疫浸润和免疫检查点的相关性。cBioPortal 数据库用于研究 ADA1 和 ADA2 的突变。LinkedOmics 用于筛选 ADA1 和 ADA2 表达相关基因。

结果：ADA1 在几种肿瘤组织中显著增加，包括胆管癌（CHOL）、弥漫性大 B 细胞淋巴瘤（DLBC）、头颈部鳞状细胞癌（HNSC）、肾透明细胞癌（KIRC）、卵巢浆液性囊腺癌（OV）、胰腺腺癌（PAAD）、胸腺瘤（THYM）和子宫癌肉瘤（UCS）。ADA2 表达在食管鳞状细胞癌（ESCA）、多形性成胶质细胞瘤（GBM）、急性髓细胞白血病（LAML）、OV、PAAD、皮肤黑色素瘤（SKCM）和胃腺癌（STAD）中显著增加。大多数癌症中血清 ADA1 活性没有明显变化，而大多数癌症中血清 ADA2 活性增加。就预后而言，ADA1 高表达与 ESCC、HNSC、KIRC、肾乳头状细胞癌（KIRP）、肝肝细胞癌（LIHC）、肺腺癌（LUAD）和子宫体子宫内膜癌（UCEC）等多种癌症的不良生存相关。然而，ADA2 高表达在乳腺癌浸润性癌（BRCA）、宫颈鳞状细胞癌和子宫内膜腺癌（CESC）、HNSC、KIRC、KIRP、LUAD、OV、PAAD、肉瘤和 THYM 中显示出有利的预后。ADA1 在大多数癌症中与多种浸润性免疫细胞呈中度正相关。ADA2 与 B 细胞、CD8 T 细胞、单核细胞/巨噬细胞和树突状细胞（DC）呈正相关，与髓系来源的抑制细胞呈强烈负相关。功能分析表明，ADA1 表达相关基因主要富集在细胞分裂的生物学进展中。然而，ADA2 相关基因主要与免疫反应相关。

结论：作为同工酶，ADA1 和 ADA2 表现出相反的预后价值，并与免疫浸润呈不同的相关性。这些数据表明 ADA1 和 ADA2 在癌症中具有不同的作用。ADA2 可能在癌症中起保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/e5a6ae2eec4f/fimmu-13-903461-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/560907e17f00/fimmu-13-903461-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/c765b3edad1f/fimmu-13-903461-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/96db05e22de1/fimmu-13-903461-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/87cc84720140/fimmu-13-903461-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/bd54abeab234/fimmu-13-903461-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/2822b67ae7a6/fimmu-13-903461-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/bef4bba25025/fimmu-13-903461-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/e5a6ae2eec4f/fimmu-13-903461-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/560907e17f00/fimmu-13-903461-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/c765b3edad1f/fimmu-13-903461-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/96db05e22de1/fimmu-13-903461-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/87cc84720140/fimmu-13-903461-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/bd54abeab234/fimmu-13-903461-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/2822b67ae7a6/fimmu-13-903461-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/bef4bba25025/fimmu-13-903461-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/70ff/9157497/e5a6ae2eec4f/fimmu-13-903461-g008.jpg

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