A four-gene signature in the tumor microenvironment that significantly associates with the prognosis of patients with breast cancer
GENE
Authors: Wang, Jianxin; Yang, Zhuowen; Zhang, Chunmei; Ouyang, Jiabao; Zhang, Guangchen; Wu, Changjun
Abstract
Breast cancer (BRCA) is a highly heterogeneous disease due to the complicated microenvironment in the tumor, making the treatment benefits varied. Therefore, this study aims to identify a gene signature in the tumor microenvironment (TME) associated with the prognosis of BRCA patients. We downloaded the immune, stromal, and proliferation (ISP)-associated genes from the literature on BRCA. mRNA expression and clinical information obtained from The Cancer Genome Atlas (TCGA) were performed to identify the initial biomarker. Furthermore, we validated the robustness of the gene signature in the independent validation data set GSE20685. A four-gene signature in TME, including CD74, MMP9, RPA3, and SHCBP1, was constructed to predict the overall survival of BRCA. The survival time of the high-risk group was significantly worse than that of the low-risk group. Univariate and multivariate Cox regression analysis showed that our four-gene ISP signature was an independent prognostic factor in TCGA and GSE20685 data sets. The AUC suggested that our four-gene ISP signature was comparable to TNM classification at predicting the overall survival of BRCA patients. Interestingly, BRCA patients with high-risk scores were more likely to be associated with stromal and proliferation of cancer. In contrast, those with high-risk scores were more likely to be associated with tumor immunity-related pathway. We found an innovative biomarker in TME to predict the prognosis of BRCA. This signal might reflect the imbalance of TME and provide potential biomarkers for the individualized and precise treatment of BRCA.
Characterisation of 22445 patients attending UK emergency departments with suspected COVID-19 infection: Observational cohort study
PLOS ONE
Authors: Goodacre, Steve; Thomas, Ben; Lee, Ellen; Sutton, Laura; Loban, Amanda; Waterhouse, Simon; Simmonds, Richard; Biggs, Katie; Marincowitz, Carl; Schutter, Jose; Connelly, Sarah; Sheldon, Elena; Hall, Jamie; Young, Emma; Bentley, Andrew; Challen, Kirsty; Fitzsimmons, Chris; Harris, Tim; Lecky, Fiona; Lee, Andrew; Maconochie, Ian; Walter, Darren
Abstract
Background Hospital emergency departments play a crucial role in the initial assessment and management of suspected COVID-19 infection. This needs to be guided by studies of people presenting with suspected COVID-19, including those admitted and discharged, and those who do not ultimately have COVID-19 confirmed. We aimed to characterise patients attending emergency departments with suspected COVID-19, including subgroups based on sex, ethnicity and COVID-19 test results. Methods and findings We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. Outcomes were admission to hospital, COVID-19 result, organ support (respiratory, cardiovascular or renal), and death, by record review at 30 days. Mean age was 58.4 years, 11200 (50.4%) were female and 11034 (49.6%) male. Adults (age >16 years) were acutely unwell (median NEWS2 score of 4), frequently had limited performance status (46.9%) and had high rates of admission (67.1%), COVID-19 positivity (31.2%), organ support (9.8%) and death (15.5%). Children had much lower rates of admission (27.4%), COVID-19 positivity (1.2%), organ support (1.4%) and death (0.3%). Similar numbers of men and women presented to the ED, but men were more likely to be admitted (72.9% v 61.4%), require organ support (12.2% v 7.7%) and die (18.2% v 13.0%). Black or Asian adults tended to be younger than White adults (median age 54, 50 and 67 years), were less likely to have impaired performance status (43.1%, 26.8% and 51.6%), be admitted to hospital (60.8%, 57.3%, 69.6%) or die (11.6%, 11.2%, 16.4%), but were more likely to require organ support (15.9%, 14.3%, 8.9%) or have a positive COVID-19 test (40.8%, 42.1%, 30.0%). Adults admitted with suspected and confirmed COVID-19 had similar age, performance status and comorbidities (except chronic lung disease) to those who did not have COVID-19 confirmed, but were much more likely to need organ support (22.2% v 8.9%) or die (32.1% v 15.5%). Conclusions Important differences exist between patient groups presenting to the emergency department with suspected COVID-19. Adults and children differ markedly and require different approaches to emergency triage. Admission and adverse outcome rates among adults suggest that policies to avoid unnecessary ED attendance achieved their aim. Subsequent COVID-19 confirmation confers a worse prognosis and greater need for organ support.