Objective: To explore the expression level and prognostic significance of erythropoietin receptor(EPOR) in patients with breast cancer(BRCA) based on estrogen receptor(ER) status and different molecular subtypes. Meth...Objective: To explore the expression level and prognostic significance of erythropoietin receptor(EPOR) in patients with breast cancer(BRCA) based on estrogen receptor(ER) status and different molecular subtypes. Methods: The Cancer Genome Atlas(TCGA) and GTEx data were collected in GEPIA initially to identify the dysregulated genes. Further, bc-GenExMiner 4.1 online bioinformatics tool was used to evaluate EPOR mRNA differential expression level according to different classification of clinicopathologic parameters in patients with breast cancer. Additionally, the prognostic value between EPOR mRNA expression and free survival of metastatic relapse(MR) or any event(AE, namely any relapse or death) in patients with breast cancer was done. Results: EPOR mRNA was significantly downregulated in BRCA(1 085 cases) compared to normal tissues(291 cases)(P<0.05). Univariate Cox analysis revealed that high EPOR mRNA expression was remarkably correlated to a decreased risk of MR(HR: 0.79, P<0.000 1) and AE(HR: 0.87, P=0.000 7) especially in breast cancer patients with ER+. Besides, high EPOR mRNA level also associated with a favorable MRfree survival(HR: 0.81, P=0.007 2) and AE-free survival(HR: 0.88, P =0.029 9) in ER+ breast cancer patients. However, no similar above phenomenon was detected in ER-patients. Moreover, the subsequent prognostic adjusted analyses and univariate Cox analysis of AE based on SSP or SCM molecular subtypes validated the above results. Conclusion: EPOR mRNA level is a valuable prognostic indicator for patients with ER+ breast cancer.展开更多
Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dih...Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the kidneys.This study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by CIH.We exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH session.Additionally,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular injection.Cognitive function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron microscopy.Oxidative stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western blotting.To further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 h.Our results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in mice.Specifically,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling pathway.Conversely,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH conditions.These findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.展开更多
基金Department of Medical Oncology,The First Affiliated Hospital of University of Science and Technology of China
文摘Objective: To explore the expression level and prognostic significance of erythropoietin receptor(EPOR) in patients with breast cancer(BRCA) based on estrogen receptor(ER) status and different molecular subtypes. Methods: The Cancer Genome Atlas(TCGA) and GTEx data were collected in GEPIA initially to identify the dysregulated genes. Further, bc-GenExMiner 4.1 online bioinformatics tool was used to evaluate EPOR mRNA differential expression level according to different classification of clinicopathologic parameters in patients with breast cancer. Additionally, the prognostic value between EPOR mRNA expression and free survival of metastatic relapse(MR) or any event(AE, namely any relapse or death) in patients with breast cancer was done. Results: EPOR mRNA was significantly downregulated in BRCA(1 085 cases) compared to normal tissues(291 cases)(P<0.05). Univariate Cox analysis revealed that high EPOR mRNA expression was remarkably correlated to a decreased risk of MR(HR: 0.79, P<0.000 1) and AE(HR: 0.87, P=0.000 7) especially in breast cancer patients with ER+. Besides, high EPOR mRNA level also associated with a favorable MRfree survival(HR: 0.81, P=0.007 2) and AE-free survival(HR: 0.88, P =0.029 9) in ER+ breast cancer patients. However, no similar above phenomenon was detected in ER-patients. Moreover, the subsequent prognostic adjusted analyses and univariate Cox analysis of AE based on SSP or SCM molecular subtypes validated the above results. Conclusion: EPOR mRNA level is a valuable prognostic indicator for patients with ER+ breast cancer.
基金This work was supported by the National Natural Science Foundation of China(No.82274617)the Hebei Natural Science Foundation(Nos.H2022423352,H2022423370)+2 种基金the Fundamental Research Funds for the Provisional Universities of Hebei University of Chinese Medicine(No.YXTD2021005)Yanzhao Medical Research Project of Hebei University of Chinese Medicine(No.YZZY2022004)the Graduate Innovation Fund of Hebei University of Chinese Medicine(No.XCXZZSS2021005)。
文摘Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the kidneys.This study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by CIH.We exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH session.Additionally,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular injection.Cognitive function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron microscopy.Oxidative stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western blotting.To further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 h.Our results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in mice.Specifically,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling pathway.Conversely,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH conditions.These findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.
