Abstract:
BACKGROUND:Castration-resistant prostate cancer (CRPC) is associated with wide variations in survival. Recent studies of whole blood mRNA expression-based biomarkers strongly predicted survival but the genes used in these biomarker models were non-overlapping and their relationship was unknown. We developed a biomarker model for CRPC that is robust, but also captures underlying biological processes that drive prostate cancer lethality. METHODS:Using three independent cohorts of CRPC patients, we developed an integrative genomic approach for understanding the biological processes underlying genes associated with cancer progression, constructed a novel four-gene model that captured these changes, and compared the performance of the new model with existing gene models and other clinical parameters. RESULTS:Our analysis revealed striking patterns of myeloid- and lymphoid-specific distribution of genes that were differentially expressed in whole blood mRNA profiles: up-regulated genes in patients with worse survival were overexpressed in myeloid cells, whereas down-regulated genes were noted in lymphocytes. A resulting novel four-gene model showed significant prognostic power independent of known clinical predictors in two independent datasets totaling 90 patients with CRPC, and was superior to the two existing gene models. CONCLUSIONS:Whole blood mRNA profiling provides clinically relevant information in patients with CRPC. Integrative genomic analysis revealed patterns of differential mRNA expression with changes in gene expression in immune cell components which robustly predicted the survival of CRPC patients. The next step would be validation in a cohort of suitable size to quantify the prognostic improvement by the gene score upon the standard set of clinical parameters.
journal_name
BMC Medjournal_title
BMC medicineauthors
Wang L,Gong Y,Chippada-Venkata U,Heck MM,Retz M,Nawroth R,Galsky M,Tsao CK,Schadt E,de Bono J,Olmos D,Zhu J,Oh WKdoi
10.1186/s12916-015-0442-0subject
Has Abstractpub_date
2015-08-21 00:00:00pages
201issn
1741-7015pii
10.1186/s12916-015-0442-0journal_volume
13pub_type
杂志文章相关文献
BMC Medicine文献大全abstract:BACKGROUND:Since the late 1980s, genetic discrimination has remained one of the major concerns associated with genetic research and clinical genetics. Europe has adopted a plethora of laws and policies, both at the regional and national levels, to prevent insurers from having access to genetic information for underwrit...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-11-25
更新日期:2013-01-31 00:00:00
abstract::The Mediterranean diet has been linked to a number of health benefits, including reduced mortality risk and lower incidence of cardiovascular disease. Definitions of the Mediterranean diet vary across some settings, and scores are increasingly being employed to define Mediterranean diet adherence in epidemiological st...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/1741-7015-12-112
更新日期:2014-07-24 00:00:00
abstract:BACKGROUND:Clinicians have known for centuries that there is substantial variability between patients in their response to medications-some individuals exhibit a miraculous recovery while others fail to respond at all. Still others experience dangerous side effects. The hunt for the factors responsible for this variati...
journal_title:BMC medicine
pub_type: 社论
doi:10.1186/s12916-016-0622-6
更新日期:2016-05-04 00:00:00
abstract:BACKGROUND:Risk stratification and management of acute myocardial infarction patients continue to be challenging despite considerable efforts made in the last decades by many clinicians and researchers. The aim of this study was to investigate the metabolomic fingerprint of acute myocardial infarction using nuclear mag...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-018-1240-2
更新日期:2019-01-07 00:00:00
abstract::Post-stroke dementia (PSD) or post-stroke cognitive impairment (PSCI) may affect up to one third of stroke survivors. Various definitions of PSCI and PSD have been described. We propose PSD as a label for any dementia following stroke in temporal relation. Various tools are available to screen and assess cognition, wi...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/s12916-017-0779-7
更新日期:2017-01-18 00:00:00
abstract:BACKGROUND:The likelihood of recurrence in patients with breast cancer who have HER2-positive tumors is relatively high, although trastuzumab is a remarkably effective drug in this setting. Signal transducer and activator of transcription 3 protein (STAT3), a transcription factor that is persistently tyrosine-705 phosp...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-015-0416-2
更新日期:2015-08-03 00:00:00
abstract::Proteinuria is a defining criterion for the diagnosis of pre-eclampsia. The amount of protein lost per day has been thought by some to predict both maternal and fetal outcome. The systematic review of 16 primary papers including over 6700 patients by Thangaratinam and colleagues published this month in BMC Medicine su...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-7-11
更新日期:2009-03-24 00:00:00
abstract::Although prostate-specific antigen (PSA) screening has improved the detection of prostate cancer, allowing for stage migration to less advanced disease, the precise mortality benefit of early detection is unclear. This is in part due to a discrepancy between the two large randomized controlled trials comparing PSA scr...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-015-0296-5
更新日期:2015-03-24 00:00:00
abstract:BACKGROUND:Coronavirus disease 2019 (COVID-19) has infected more than 4 million people within 4 months. There is an urgent need to properly identify high-risk cases that are more likely to deteriorate even if they present mild diseases on admission. METHODS:A multicenter nested case-control study was conducted in four...
journal_title:BMC medicine
pub_type: 杂志文章,多中心研究
doi:10.1186/s12916-020-01633-7
更新日期:2020-06-03 00:00:00
abstract:BACKGROUND:Dietary assessment is complex, and strategies to select the most appropriate dietary assessment tool (DAT) in epidemiological research are needed. The DIETary Assessment Tool NETwork (DIET@NET) aimed to establish expert consensus on Best Practice Guidelines (BPGs) for dietary assessment using self-report. M...
journal_title:BMC medicine
pub_type: 杂志文章,实务指引
doi:10.1186/s12916-017-0962-x
更新日期:2017-11-15 00:00:00
abstract:BACKGROUND:Resistance and tolerance to Plasmodium falciparum can determine the progression of malaria disease. However, quantitative evidence of tolerance is still limited. We investigated variations in the adverse impact of P. falciparum infections among African pregnant women under different intensities of malaria tr...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-017-0893-6
更新日期:2017-07-17 00:00:00
abstract:BACKGROUND:Human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic myelopathy characterized by motor dysfunction of the lower extremities and urinary disturbance. Immunomodulatory treatments are the main strategy for HAM/TSP, but several issues are associated...
journal_title:BMC medicine
pub_type: 临床试验,杂志文章
doi:10.1186/1741-7015-11-182
更新日期:2013-08-15 00:00:00
abstract:BACKGROUND:The use of early morning sputum samples (EMS) to diagnose tuberculosis (TB) can result in treatment delay given the need for the patient to return to the clinic with the EMS, increasing the chance of patients being lost during their diagnostic workup. However, there is little evidence to support the superior...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-017-0947-9
更新日期:2017-10-27 00:00:00
abstract:BACKGROUND:The ability to do online searches for health information has led to concerns that patients find the results confusing and that they often lead to expectations for treatments that have little supportive evidence. At the same time, the science of summarizing research evidence has advanced to the point where it...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-015-0436-y
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:Clinical pathways are tools used to guide evidence-based healthcare that have been implemented internationally since the 1980s. However, there is widespread lack of agreement on the impact of clinical pathways on hospital resources and patient outcomes. This can be partially attributed to the confusion for b...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/1741-7015-8-31
更新日期:2010-05-27 00:00:00
abstract:BACKGROUND:The United States Preventive Services Task Force (USPSTF) recommends screening adults for depression in primary care settings when staff-assisted depression management programs are available. This recommendation, however, is based on evidence from depression management programs conducted with patients alread...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-12-13
更新日期:2014-01-28 00:00:00
abstract:BACKGROUND:The TransEurope FootRace 2009 (TEFR09) was one of the longest transcontinental ultramarathons with an extreme endurance physical load of running nearly 4,500 km in 64 days. The aim of this study was to assess the wide spectrum of adaptive responses in humans regarding the different tissues, organs and functi...
journal_title:BMC medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/1741-7015-10-78
更新日期:2012-07-19 00:00:00
abstract:BACKGROUND:The World Health Organisation (WHO) recommends parasitological diagnosis of malaria before treatment, but use of malaria rapid diagnostic tests (mRDTs) by community health workers (CHWs) has not been fully tested within health services in south and central Asia. mRDTs could allow CHWs to diagnose malaria acc...
journal_title:BMC medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12916-017-0891-8
更新日期:2017-07-07 00:00:00
abstract:BACKGROUND:A beneficial effect of a high n-3 long-chain polyunsaturated fatty acid (LCPUFA) intake has been observed in heart failure patients, who are frequently insulin resistant. We investigated the potential influence of impaired glucose metabolism on the relation between dietary intake of n-3 LCPUFAs and risk of a...
journal_title:BMC medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/1741-7015-11-216
更新日期:2013-10-08 00:00:00
abstract::Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted effort...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-10-34
更新日期:2012-04-12 00:00:00
abstract::The Ebola virus disease (EVD) outbreak in the three West Africa countries of Guinea, Liberia, and Sierra Leone, was declared by the World Health Organization (WHO) as a public health event of international concern in August 2014. The disease, which has caused more than 10,000 deaths from over 25,000 cases, has thrived...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-015-0359-7
更新日期:2015-05-14 00:00:00
abstract:BACKGROUND:Smokers have been shown to have lower mortality after acute coronary syndrome than non-smokers. This has been attributed to the younger age, lower co-morbidity, more aggressive treatment and lower risk profile of the smoker. Some studies, however, have used multivariate analyses to show a residual survival b...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-9-97
更新日期:2011-08-23 00:00:00
abstract::How should we approach trial design when we can get some, but not all, of the way to the numbers required for a randomised phase III trial?We present an ordered framework for designing randomised trials to address the problem when the ideal sample size is considered larger than the number of participants that can be r...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-016-0722-3
更新日期:2016-11-25 00:00:00
abstract:BACKGROUND:Electronic mail (email) has the potential to improve communication between physicians and patients. METHODS:We conducted two research studies in a family practice setting: 1) a brief, anonymous patient survey of a convenience sample to determine the number of clinic patients receptive to communicating with ...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/1741-7015-4-18
更新日期:2006-08-15 00:00:00
abstract::Psychiatric nosology is widely criticized, but solutions are proving elusive. Planned revisions of diagnostic criteria will not resolve heterogeneity, comorbidity, fuzzy boundaries between normal and pathological, and lack of specific biomarkers. Concern about these difficulties reflects a narrow model that assumes mo...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/1741-7015-10-5
更新日期:2012-01-13 00:00:00
abstract:BACKGROUND:International medical graduates working in the UK are more likely to be censured in relation to fitness to practise compared to home graduates. Performance on the General Medical Council's (GMC's) Professional and Linguistic Assessments Board (PLAB) tests and English fluency have previously been shown to pre...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-017-0829-1
更新日期:2017-03-20 00:00:00
abstract:BACKGROUND:Virtual histology intravascular ultrasound (VH-IVUS) imaging is an innovative tool for the morphological evaluation of coronary atherosclerosis. Evidence for the effects of statin therapy on VH-IVUS parameters have been inconclusive. Consequently, we performed a systematic review and meta-analysis to investi...
journal_title:BMC medicine
pub_type: 杂志文章,meta分析,评审
doi:10.1186/s12916-015-0459-4
更新日期:2015-09-18 00:00:00
abstract:BACKGROUND:Involving adults lacking capacity (ALC) in research on end of life care (EoLC) or serious illness is important, but often omitted. We aimed to develop evidence-based guidance on how best to include individuals with impaired capacity nearing the end of life in research, by identifying the challenges and solut...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-020-01654-2
更新日期:2020-07-22 00:00:00
abstract:BACKGROUND:Guidelines recommend that clinicians should make brief opportunistic behavioural interventions to patients who are obese to increase the uptake of effective weight loss programmes. The objective was to assess the effect of this policy on socioeconomic equity. METHODS:One thousand eight hundred eighty-two co...
journal_title:BMC medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12916-019-1284-y
更新日期:2019-03-01 00:00:00
abstract::The Fluid Expansion as Supportive Therapy (FEAST study) was an extremely well conducted study that gave unexpected results. The investigators had reported that febrile children with impaired perfusion treated in low-income countries without access to intensive care are more likely to die if they receive bolus resuscit...
journal_title:BMC medicine
pub_type: 评论,杂志文章
doi:10.1186/1741-7015-11-67
更新日期:2013-03-14 00:00:00