RESUMEN
Although stromal fibroblasts play a critical role in cancer progression, their identities remain unclear as they exhibit high heterogeneity and plasticity. Here, a master transcription factor (mTF) constructing core-regulatory circuitry, PRRX1, which determines the fibroblast lineage with a myofibroblastic phenotype, is identified for the fibroblast subgroup. PRRX1 orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-ß signaling by remodeling a super-enhancer landscape. Such reprogrammed fibroblasts have myofibroblastic functions resulting in markedly enhanced tumorigenicity and aggressiveness of cancer. PRRX1 expression in cancer-associated fibroblast (CAF) has an unfavorable prognosis in multiple cancer types. Fibroblast-specific PRRX1 depletion induces long-term and sustained complete remission of chemotherapy-resistant cancer in genetically engineered mice models. This study reveals CAF subpopulations based on super-enhancer profiles including PRRX1. Therefore, mTFs, including PRRX1, provide another opportunity for establishing a hierarchical classification system of fibroblasts and cancer treatment by targeting fibroblasts.
Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias , Animales , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos/metabolismo , Ratones , Miofibroblastos , Neoplasias/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
AIM: We aimed to investigate the incidence rate and risk factors of medical device-related pressure injuries (MDRPIs) among patients undergoing prone position spine surgery. MATERIALS AND METHODS: This was a prospective observational study of 147 patients who underwent spine surgery in an orthopaedic hospital in Korea. The incidence of MDRPI according to intrinsic and extrinsic factors was assessed using the independent t-, χ2 -, or Fisher's exact tests. A logistic regression analysis was performed exclusively for MDRPI areas with an incidence rate >5%. RESULTS: The mean incidence rate of overall MDRPI was 27.4%, while that of MDRPI by Wilson frame, bi-spectral index, and endotracheal tube (ETT) was 56.5%, 52.4%, and 9.5%, respectively. The risk factors under Wilson frame were operation time and body mass index classification. Compared to their normal weight counterparts, those who were underweight, overweight, and obese had a 46.57(95% CI: 6.37-340.26), 3.96 (95% CI: 1.13-13.86), and 5.60 times (95% CI: 1.62-19.28) higher risk of developing MDRPI, respectively. The risk factors by bi-spectral index were sex, operation time, and the American Society of Anaesthesiologists classification. Compared to ETT intubation of <2 h, the risk of MDRPI increased by 7.16 times (95% CI: 1.35-38.00) and 7.93 times (95% CI: 1.45-43.27) for<3 and ≥3 h' duration, respectively. CONCLUSION: The difficulty of device repositioning can increase the incidence of MDRPI, and prolonged surgery was a significant risk factor. Thus, appropriate planning and correct equipment utilization is needed during prone position spine surgeries.