Interaction between HER2 and ATM predicts poor survival in bladder cancer patients.

Autor: Albarakati N; Department of Cellular Therapy and Cancer Research, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.; King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard - Health Affairs, Riyadh, Saudi Arabia., Al-Shareeda A; King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard - Health Affairs, Riyadh, Saudi Arabia.; Department of Cellular Therapy and Cancer Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia.; Department of the Saudi Biobank, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia., Ramadan M; King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard - Health Affairs, Riyadh, Saudi Arabia.; Department of Population Health Research, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia., Al-Sowayan B; King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard - Health Affairs, Riyadh, Saudi Arabia.; Department of Cellular Therapy and Cancer Research, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia., Negm O; School of Medicine, University of Nottingham, Nottingham, UK.; Microbiology and Immunology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt., Nedjadi T; Department of Cellular Therapy and Cancer Research, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.; King Saud bin Abdulaziz University for Health Sciences, Ministry of the National Guard - Health Affairs, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2022 Oct; Vol. 26 (19), pp. 4959-4973. Date of Electronic Publication: 2022 Sep 03.
DOI: 10.1111/jcmm.17512
Abstrakt: Human Epidermal Growth Factor Receptor 2 (HER2) overexpression is considered one of the interesting prognostic biomarkers in bladder cancer. However, the mechanism of bladder cancer development in relation to HER2 status remains to be elucidated. In this study, we investigated HER2-Ataxia 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-Meier survival analysis indicated that ATM low and HER2 high is a powerful prognosticator of both overall survival (OS) and disease-free 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-Akt 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.
(© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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