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ADAR 在泛癌中的临床意义、肿瘤免疫图谱和免疫治疗反应及其与膀胱癌增殖和转移的关系。

Clinical significance, tumor immune landscape and immunotherapy responses of ADAR in pan-cancer and its association with proliferation and metastasis of bladder cancer.

机构信息

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.

Institute of Urology and Andrology, Nanjing Medical University, Nanjing 210029, PR China.

出版信息

Aging (Albany NY). 2023 Jul 6;15(13):6302-6330. doi: 10.18632/aging.204853.

DOI:10.18632/aging.204853
PMID:37414093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10373965/
Abstract

BACKGROUND

ADAR is an enzyme involved in adenosine-inosine RNA editing. However, the role of ADAR in tumorigenesis, progression, and immunotherapy has not been fully elucidated.

METHODS

The TCGA, GTEx and GEO databases were extensively utilized to explore the expression level of ADAR across cancers. Combined with the clinical information of patients, the risk profile of ADAR in various cancers was delineated. We identified pathways enriched in ADAR and their related genes and explored the association between ADAR expression and the cancer immune microenvironment score and response to immunotherapy. Finally, we specifically explored the potential value of ADAR in the treatment of the bladder cancer immune response and verified the critical role of ADAR in the development and progression of bladder cancer through experiments.

RESULTS

ADAR is highly expressed in most cancers at both the RNA and protein level. ADAR is associated with the aggressiveness of some cancers, especially bladder cancer. In addition, ADAR is associated with immune-related genes, especially immune checkpoint genes, in the tumor immune microenvironment. Moreover, ADAR expression is positively correlated with tumor mutation burden and microsatellite instability in a variety of cancers, indicating that ADAR could be used as a biomarker of immunotherapy. Finally, we demonstrated that ADAR is a key pathogenic factor in bladder cancer. ADAR promoted proliferation and metastasis of bladder cancer cells.

CONCLUSION

ADAR regulates the tumor immune microenvironment and can be used as a biomarker of the tumor immunotherapy response, providing a novel strategy for the treatment of tumors, especially bladder cancer.

摘要

背景

ADAR 是一种参与腺苷-次黄嘌呤 RNA 编辑的酶。然而,ADAR 在肿瘤发生、进展和免疫治疗中的作用尚未完全阐明。

方法

广泛利用 TCGA、GTEx 和 GEO 数据库来研究 ADAR 在各种癌症中的表达水平。结合患者的临床信息,描绘 ADAR 在各种癌症中的风险特征。我们确定了 ADAR 富集的途径及其相关基因,并探讨了 ADAR 表达与癌症免疫微环境评分和对免疫治疗的反应之间的关系。最后,我们专门探讨了 ADAR 在膀胱癌免疫反应治疗中的潜在价值,并通过实验验证了 ADAR 在膀胱癌发生和发展中的关键作用。

结果

ADAR 在大多数癌症中的 RNA 和蛋白水平均高度表达。ADAR 与某些癌症的侵袭性有关,尤其是膀胱癌。此外,ADAR 与肿瘤免疫微环境中的免疫相关基因,特别是免疫检查点基因有关。此外,ADAR 表达与多种癌症中的肿瘤突变负担和微卫星不稳定性呈正相关,表明 ADAR 可作为免疫治疗的生物标志物。最后,我们证明 ADAR 是膀胱癌的一个关键致病因素。ADAR 促进了膀胱癌细胞的增殖和转移。

结论

ADAR 调节肿瘤免疫微环境,可作为肿瘤免疫治疗反应的生物标志物,为肿瘤的治疗,特别是膀胱癌的治疗提供了新策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/a4d44d486469/aging-15-204853-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/261910a74e6b/aging-15-204853-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/39132b7f9f7b/aging-15-204853-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/a9bd5045b39e/aging-15-204853-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/f38a6a542eec/aging-15-204853-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/d18cdd6e1880/aging-15-204853-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/719477fab0fc/aging-15-204853-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/8d8abb8a1870/aging-15-204853-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/1a0b99f8906f/aging-15-204853-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/a4d44d486469/aging-15-204853-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/261910a74e6b/aging-15-204853-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/39132b7f9f7b/aging-15-204853-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/a9bd5045b39e/aging-15-204853-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/f38a6a542eec/aging-15-204853-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/d18cdd6e1880/aging-15-204853-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/719477fab0fc/aging-15-204853-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/8d8abb8a1870/aging-15-204853-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/1a0b99f8906f/aging-15-204853-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81a7/10373965/a4d44d486469/aging-15-204853-g009.jpg

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