{"title":"The ADRB1 (Adrenoceptor Beta 1) and ADRB2 genes significantly co-express with commonly mutated genes in prostate cancer.","authors":"Steven Lehrer, Peter H Rheinstein","doi":"","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Beta blockers act on the beta-adrenergic receptors ADRB1 and ADRB2 to reduce heart rate and blood pressure. Observational studies have revealed strong risk reductions in metastasis and cancer-specific mortality with the use of beta-blockers in patients with some cancers. But observational studies of prostate cancer have reported conflicting results.</p><p><strong>Objectives: </strong>We examined the relationship of ADRB1 (Adrenoceptor beta 1) gene expression and ADRB2 (Adrenoceptor beta 2) gene expression with Forkhead box protein A1 (FOXA1) gene expression in prostate cancer. We also analyzed survival data of solid tumor patients with respect to beta 1 (ADRB1) and beta 2 (ADRB2) adrenergic receptor gene expression.</p><p><strong>Methods: </strong>We examined the genomics of prostate cancer and other solid primary tumors in the GDC TCGA Prostate Cancer (PRAD) data set. The Cancer Genome Atlas (TCGA) contains the analysis of over 11,000 tumors from 33 of the most prevalent forms of cancer.</p><p><strong>Results: </strong>The presence of somatic mutations [Single nucleotide polymorphisms (SNPs) and small insertion/deletion polymorphism (INDELS)] in FOXA1 alters ADRB1 and ADRB2 gene expression. The correlation of FOXA1 gene expression with ADRB1 and ADRB2 gene expression is highly significant. Alterations in FOXA1 genes, ADRB1 genes, and ADRB2 genes are significantly co-occurrent, indicating that they may work in tandem to drive tumor formation and development. Increased ADRB1 and ADRB2 expressions reduce the overall survival of solid tumor patients in the GDC Pan Cancer set.</p><p><strong>Conclusions: </strong>FOXA1 signaling may regulate ADRB1 and ADRB2 expression, as well as androgen receptor expression. Analysis of these tumor mutations might indicate whether an individual prostate cancer patient will respond to beta blockers.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":"30 161","pages":"163-171"},"PeriodicalIF":2.0000,"publicationDate":"2020-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894950/pdf/nihms-1661705.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Discovery medicine","FirstCategoryId":"3","ListUrlMain":"","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Beta blockers act on the beta-adrenergic receptors ADRB1 and ADRB2 to reduce heart rate and blood pressure. Observational studies have revealed strong risk reductions in metastasis and cancer-specific mortality with the use of beta-blockers in patients with some cancers. But observational studies of prostate cancer have reported conflicting results.
Objectives: We examined the relationship of ADRB1 (Adrenoceptor beta 1) gene expression and ADRB2 (Adrenoceptor beta 2) gene expression with Forkhead box protein A1 (FOXA1) gene expression in prostate cancer. We also analyzed survival data of solid tumor patients with respect to beta 1 (ADRB1) and beta 2 (ADRB2) adrenergic receptor gene expression.
Methods: We examined the genomics of prostate cancer and other solid primary tumors in the GDC TCGA Prostate Cancer (PRAD) data set. The Cancer Genome Atlas (TCGA) contains the analysis of over 11,000 tumors from 33 of the most prevalent forms of cancer.
Results: The presence of somatic mutations [Single nucleotide polymorphisms (SNPs) and small insertion/deletion polymorphism (INDELS)] in FOXA1 alters ADRB1 and ADRB2 gene expression. The correlation of FOXA1 gene expression with ADRB1 and ADRB2 gene expression is highly significant. Alterations in FOXA1 genes, ADRB1 genes, and ADRB2 genes are significantly co-occurrent, indicating that they may work in tandem to drive tumor formation and development. Increased ADRB1 and ADRB2 expressions reduce the overall survival of solid tumor patients in the GDC Pan Cancer set.
Conclusions: FOXA1 signaling may regulate ADRB1 and ADRB2 expression, as well as androgen receptor expression. Analysis of these tumor mutations might indicate whether an individual prostate cancer patient will respond to beta blockers.
期刊介绍：
Discovery Medicine publishes novel, provocative ideas and research findings that challenge conventional notions about disease mechanisms, diagnosis, treatment, or any of the life sciences subjects. It publishes cutting-edge, reliable, and authoritative information in all branches of life sciences but primarily in the following areas: Novel therapies and diagnostics (approved or experimental); innovative ideas, research technologies, and translational research that will give rise to the next generation of new drugs and therapies; breakthrough understanding of mechanism of disease, biology, and physiology; and commercialization of biomedical discoveries pertaining to the development of new drugs, therapies, medical devices, and research technology.
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