ABSTRACT
BACKGROUND: Peroxiredoxin 1 (PRDX1) belongs to an abundant family of peroxidases whose role in cancer is still unresolved. While mouse knockout studies demonstrate a tumour suppressive role for PRDX1, in cancer cell xenografts, results denote PRDX1 as a drug target. Probably, this phenotypic discrepancy stems from distinct roles of PRDX1 in certain cell types or stages of tumour progression. METHODS: We demonstrate an important cell-autonomous function for PRDX1 utilising a syngeneic mouse model (BALB/c) and mammary fibroblasts (MFs) obtained from it. RESULTS: Loss of PRDX1 in vivo promotes collagen remodelling known to promote breast cancer progression. PRDX1 inactivation in MFs occurs via SRC-induced phosphorylation of PRDX1 TYR194 and not through the expected direct oxidation of CYS52 in PRDX1 by ROS. TYR194-phosphorylated PRDX1 fails to bind to lysyl oxidases (LOX) and leads to the accumulation of extracellular LOX proteins which supports enhanced collagen remodelling associated with breast cancer progression. CONCLUSIONS: This study reveals a cell type-specific tumour suppressive role for PRDX1 that is supported by survival analyses, depending on PRDX1 protein levels in breast cancer cohorts.
Subject(s)
Breast Neoplasms/pathology , Extracellular Matrix/metabolism , Peroxiredoxins/metabolism , Protein-Lysine 6-Oxidase/metabolism , Tyrosine/metabolism , Animals , Breast Neoplasms/metabolism , Cell Line, Tumor , Collagen/metabolism , Female , Gene Expression Regulation, Neoplastic , HEK293 Cells , Humans , Mice , Phosphorylation , Prognosis , Survival AnalysisABSTRACT
BACKGROUND: Interfacility transfers between emergency department (EDs) are common and at times unnecessary. We sought to examine the role of health insurance status with potentially avoidable transfers. METHODS: We conducted a retrospective observational analysis using hospital electronic administrative data of all interfacility ED-to-ED transfers to a single, quaternary care adult ED in 2018. We defined a potentially avoidable transfer as an ED-to-ED transfer in which the patient did not receive a procedure from a specialist at the receiving hospital and was discharged from the ED or the receiving hospital within 24 hours of arrival. We constructed a multivariable logistic regression model to examine whether insurance status was associated with potentially avoidable transfers among all ED-to-ED transfers adjusting for patient demographics, severity, mode of arrival, clinical condition, and rurality. RESULTS: Among 7508 transfers, 1862 (25%) were potentially avoidable and were more likely to be uninsured (20% vs 9%). In the multivariable analysis, among ED-to-ED transfers for adults aged 18-64 years old who were uninsured (vs any insurance) were significantly more likely to be potentially avoidable (adjusted odds ratio [aOR] 2.1 [1.7, 2.4]) and there is a significant interaction with age. Potentially avoidable transfers increased with younger age, male sex, black (vs white), small rural classification (vs urban), and arrival by ground ambulance (vs flight). CONCLUSIONS: Potentially avoidable transfers comprised 1 in 4 transfers. Patients who lack insurance were more than twice as likely to be classified as potentially avoidable even after evaluating for confounders and interactions. This effect was most pronounced among younger patients. Further research is needed to explore why uninsured patients are disproportionately more likely to experience potentially avoidable transfers.
