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However, the mechanism of bladder cancer development in relation to HER2 status remains to be elucidated. In this study, we investigated HER2\u2010Ataxia telangiectasia mutated (ATM) kinase interaction and their impact on patient survival and cancer aggressiveness. Using the Cancer Genome Atlas (TCGA) cohorts, we demonstrated that ATM expression (protein\/mRNA) is increased in HER2 deficient compared with proficient HER2 patients. This finding was then validated using the Gene Expression Omnibus database (GEO). Correlation analysis (using low expression vs high expression as a discriminator) revealed a significant association of ATM low and HER2 high status with several clinicopathological variables such as high tumour grade, late disease stage and tumour shape. Kaplan\u2013Meier survival analysis indicated that ATM low and HER2 high is a powerful prognosticator of both overall survival (OS) and disease\u2010free survival (DFS). Furthermore, using bioinformatics and protein\/protein interaction analyses, we identified 66 putative overlapping proteins with direct link between HER2 and ATM most of which are functionally involved in transcription regulation, apoptotic process and cell proliferation. Interestingly, the results showed that these proteins are strongly linked with PI3K\u2010Akt pathway, p53 pathway and microRNAs in cancer. Altogether, our data pinpoint an important biological role of the interconnection between HER2 and ATM. The latter appear to be an independent prognostic biomarker and may serve as targets to develop novel combination therapies to improve the outcome of patients with bladder cancer.<\/jats:p>","DOI":"10.1111\/jcmm.17512","type":"journal-article","created":{"date-parts":[[2022,9,3]],"date-time":"2022-09-03T07:40:55Z","timestamp":1662190855000},"page":"4959-4973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Interaction between <scp>HER2<\/scp> and <scp>ATM<\/scp> predicts poor survival in bladder cancer patients"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-8684","authenticated-orcid":false,"given":"Nada","family":"Albarakati","sequence":"first","affiliation":[{"name":"Department of Cellular Therapy and Cancer Research King Abdullah International Medical Research Center  Jeddah Saudi Arabia"},{"name":"King Saud bin Abdulaziz University for Health Sciences, Ministry of the 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