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1.
Immunol Invest ; : 1-17, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31854233

RESUMO

Background: Gly307Ser (rs763361) polymorphism in Cluster of Differentiation 226 (CD226) gene has been implicated in susceptibility to autoimmune diseases (ADs) with controversial results. This study aimed to conduct a meta-analysis for examining the relationship between CD226 rs763361 polymorphism and ADs risk.Methods: a literature search was performed to identify relevant studies published in Embase, PubMed, Wanfang, and China National Knowledge Infrastructure. In the most appropriate genetic models, pooled odds ratio (OR) with 95% confidence interval (CI) was calculated for evaluating the strength of the associations. Besides standard meta-analysis, cumulative meta-analysis was also conducted to assess the trend in OR over time. Also, we performed subgroup and sensitivity analysis, and checked for the heterogeneity and publication bias.Results: Twenty-nine reports with 51 independent studies, comprising 18157 cases and 29904 controls, were enrolled in this meta-analysis. Among overall and various ethnic populations (Europeans, Asians, Africans, and South Americans), CD226 rs763361 polymorphism was significantly associated with ADs susceptibility; in the subgroup analysis by disease type, rs763361 polymorphism revealed significant associations with the risk of RA, SLE, T1D, and MS. The sensitivity analysis and cumulative meta-analysis confirmed the stability and robustness of these significant results. However, no evidence of stable significant association emerged in the subgroup analysis of SSc.Conclusion: These findings demonstrate that CD226 rs763361 polymorphism confers susceptibility to ADs in the overall population, Europeans, Asians, Africans, and South Americans. rs763361 polymorphism in CD226 gene may be a potential susceptible predictor of ADs especially RA, SLE, T1D, and MS.

2.
Ther Adv Respir Dis ; 13: 1753466619888124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31722614

RESUMO

BACKGROUND: Sepsis and septic shock are common in noninvasive ventilation (NIV) patients. However, studies on the association between sepsis and NIV failure are lacking. METHODS: A prospective multi-center observational study was performed in 16 Chinese intensive care units (ICUs). Patients who used NIV due to hypoxemic respiratory failure were enrolled. Sepsis and septic shock were diagnosed according to the guideline of sepsis-3. RESULTS: A total of 519 patients were enrolled. Sepsis developed in 365 patients (70%) and septic shock developed in 79 patients (15%). However, 75 patients (14%) had no sepsis. NIV failure was 23%, 38%, and 61% in patients, with no sepsis, sepsis, and septic shock, respectively. Multivariate analysis found that sepsis [odds ratio (OR) = 1.95, 95% confidence interval (CI): 1.06-3.61] and septic shock (OR = 2.47, 95% CI: 1.12-5.45) were independently associated with NIV failure. In sepsis and septic shock population, the NIV failure was 13%, 31%, 37%, 53%, and 67% in patients with sequential organ failure assessment (SOFA) scores of ⩽2, 3-4, 5-6, 7-8, and ⩾9, respectively. Patients with nonpulmonary induced sepsis had similar NIV failure rate compared with those with pulmonary induced sepsis, but had higher proportion of septic shock (37% versus 10%, p ⩽ 0.01) and lower ICU mortality (10% versus 22%, p ⩽ 0.01). CONCLUSIONS: Sepsis was associated with NIV failure in patients with hypoxemic respiratory failure, and the association was stronger in septic shock patients. NIV failure increased with the increase of organ dysfunction caused by sepsis. The reviews of this paper are available via the supplemental material section.

3.
Ann Intensive Care ; 9(1): 108, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31565779

RESUMO

BACKGROUND: Early identification of noninvasive ventilation (NIV) failure is a promising strategy for reducing mortality in chronic obstructive pulmonary disease (COPD) patients. However, a risk-scoring system is lacking. METHODS: To develop a scale to predict NIV failure, 500 COPD patients were enrolled in a derivation cohort. Heart rate, acidosis (assessed by pH), consciousness (assessed by Glasgow coma score), oxygenation, and respiratory rate (HACOR) were entered into the scoring system. Another two groups of 323 and 395 patients were enrolled to internally and externally validate the scale, respectively. NIV failure was defined as intubation or death during NIV. RESULTS: Using HACOR score collected at 1-2 h of NIV to predict NIV failure, the area under the receiver operating characteristic curves (AUC) was 0.90, 0.89, and 0.71 for the derivation, internal-validation, and external-validation cohorts, respectively. For the prediction of early NIV failure in these three cohorts, the AUC was 0.91, 0.96, and 0.83, respectively. In all patients with HACOR score > 5, the NIV failure rate was 50.2%. In these patients, early intubation (< 48 h) was associated with decreased hospital mortality (unadjusted odds ratio = 0.15, 95% confidence interval 0.05-0.39, p < 0.01). CONCLUSIONS: HACOR scores exhibited good predictive power for NIV failure in COPD patients, particularly for the prediction of early NIV failure (< 48 h). In high-risk patients, early intubation was associated with decreased hospital mortality.

4.
Immunol Invest ; 48(6): 563-576, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31044630

RESUMO

Background: Polymorphisms in T-cell immunoglobulin and mucin domain 3 (TIM-3) gene have been implicated in susceptibility to autoimmune diseases (ADs) with inconsistent results. The aim of this study was to perform meta-analyses for clarifying the relationship between them. Methods: All relevant case-control studies were searched in PubMed, Embase, Wanfang, and China National Knowledge Infrastructure. Meta-analysis was conducted in the dominant and allelic models, and checked for heterogeneity and publication bias. The Odds ratio (OR) and 95% confidence interval (CI) was used to assess the strength of the associations. Results: Seventeen studies with four TIM-3 polymorphisms (+4259A>C, -574G>T, -1516G>T, and -1541C>T) were identified, involving 3,399 cases and 3,911 controls. TIM-3 -1516G>T polymorphism showed significant associations with ADs risk among Chinese; however, the significant finding was unstable in sensitivity analysis. In the overall population, TIM-3 + 4259A>C polymorphism demonstrated stable significant associations with ADs risk in the dominant (OR = 1.57, 95%CI = 1.13-2.18, P = 0.007) and allelic (OR = 1.51, 95%CI = 1.10-2.08, P = 0.01) models, and with rheumatoid arthritis (RA) risk in the dominant (OR = 2.09, 95%CI = 1.60-2.73, P < 0.00001) and allelic (OR = 1.95, 95%CI = 1.51-2.51, P < 0.00001) models. Cumulative meta-analyses confirmed that these significant results were robust. Concerning TIM-3 -574 G > T or -1541C>T polymorphism, no significant associations were detected. Conclusion: These findings reveal that TIM-3 + 4259A>C might be a potential susceptible predictor of ADs and especially RA. Further functional and clinical investigation between these diseases and TIM-3 polymorphisms is warranted.


Assuntos
Artrite Reumatoide/genética , Doenças Autoimunes/genética , Genótipo , Receptor Celular 2 do Vírus da Hepatite A/genética , Estudos de Casos e Controles , China , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Polimorfismo Genético , Fatores de Risco
5.
J Crit Care ; 50: 77-81, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30500567

RESUMO

PURPOSE: Prophylactic noninvasive ventilation (NIV) reduces re-intubation in high-risk patients. However, its effects in elderly patients remain unclear. Here, we investigated the efficacy of prophylactic NIV in elderly patients after a planned extubation. MATERIALS AND METHODS: From January 2011 to December 2017, patients aged ≥65 years old were enrolled after completing an SBT. After extubation, patients who immediately received NIV were classified as the prophylactic NIV group, and those who did not were classified as the control group. Re-intubation was recorded at postextubation 72 h. RESULTS: We enrolled 171 and 120 patients in the NIV and control groups, respectively. Patients in the NIV group had a lower re-intubation rate (6.4% vs. 23.3%, p < 0.01) and lower hospital mortality (22.2% vs. 35.8%, p = 0.01) than controls. In addition, prophylactic NIV was an independent protective factor for re-intubation (OR = 0.15, 95% CI: 0.07-0.34, p < 0.01 for all patients; OR = 0.16, 95% CI: 0.05-0.52, p < 0.01 for AECOPD patients, and OR = 0.17, 95% CI: 0.05-0.62, p < 0.01 for pneumonia/ARDS patients). After completing propensity-matched analyses, prophylactic NIV also reduced re-intubation and hospital mortality. CONCLUSIONS: Elderly patients received benefits from prophylactic NIV after a planned extubation.

6.
BMJ Open ; 8(12): e019271, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30518577

RESUMO

OBJECTIVE: To report the resource use, characteristics and outcomes of patients with prolonged non-invasive ventilation (NIV). DESIGN: A single-centre observational study. SETTING: An intensive care unit of a teaching hospital. PARTICIPANTS: Patients who only received NIV because of acute respiratory failure were enrolled. Prolonged NIV was defined as subjects who received NIV ≥14 days. A total of 1539 subjects were enrolled in this study; 69 (4.5%) underwent prolonged NIV. MAIN OUTCOME MEASURES: Predictors of prolonged NIV and hospital mortality. RESULTS: The rate of do-not-intubate (DNI) orders was 9.1% (140/1539). At the beginning of NIV, a DNI order (OR 3.95, 95% CI 2.25 to 6.95) and pH ≥7.35 (2.20, 1.27 to 3.82) were independently associated with prolonged NIV. At days 1 and 7 of NIV, heart rate (1.01 (1.00 to 1.03) and 1.02 (1.00 to 1.03], respectively) and PaO2/FiO2<150 (2.19 (1.25 to 3.85) and 2.05 (1.04 to 4.04], respectively) were other independent risk factors for prolonged NIV. When patients who died after starting NIV but prior to 14 days were excluded, the association was strengthened. Regarding resource use, 77.1% of subjects received NIV<7 days and only accounted for 47.0% of NIV-days. However, 18.4% of subjects received NIV 7-13.9 days and accounted for 33.4% of NIV-days, 2.9% of subjects received NIV 14-20.9 days and accounted for 9.5% of NIV-days, and 1.6% of subjects received NIV≥21 days and accounted for 10.1% of NIV-days. CONCLUSIONS: Our results indicate the resource use, characteristics and outcomes of a prolonged NIV population with a relatively high proportion of DNI orders. Subjects with prolonged NIV make up a high proportion of NIV-days and are at high risk for in-hospital mortality.


Assuntos
Mortalidade Hospitalar , Ventilação não Invasiva/estatística & dados numéricos , Insuficiência Respiratória/terapia , Idoso , China , Feminino , Frequência Cardíaca , Humanos , Concentração de Íons de Hidrogênio , Unidades de Terapia Intensiva , Masculino , Oxigênio/análise , Insuficiência Respiratória/mortalidade , Ordens quanto à Conduta (Ética Médica) , Fatores de Tempo
7.
J Crit Care ; 44: 149-153, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29128779

RESUMO

PURPOSE: To explore the association between cough strength and outcomes in elderly patients who received noninvasive ventilation (NIV) due to acute respiratory failure caused by pneumonia. MATERIALS AND METHODS: We enrolled patients ≥65years old with acute respiratory failure caused by pneumonia. Just before NIV treatment, cough strength was assessed on a cough-strength scale graded from 0 to 5. Patients graded 0-2 were defined as having no/weak coughs and those graded 3-5 were defined as having moderate/strong coughs. RESULTS: We enrolled 349 patients in this study. The prevalence of no/weak cough was 24% (84/349). Moderate/strong cough patients had lower NIV failure (92/265 [34.7%] vs. 67/84 [79.8%], p<0.01) and lower hospital mortality (85/265 [32.1%] vs. 60/84 [71.4%], p<0.01) than no/weak cough patients. In multivariate logistic regression analysis, we also found that no/weak cough was an independent risk factor for NIV failure (odds ratio=13.83, 95% confidence interval: 6.01-31.81) and death in hospital (odds ratio=4.41, 95% confidence interval: 2.49-7.81). CONCLUSIONS: In pneumonia patients ≥65years old, no/weak cough is associated with NIV failure and death in hospital. NIV must be used only with caution in no/weak cough patients.


Assuntos
Tosse/diagnóstico , Ventilação não Invasiva , Pneumonia/terapia , Insuficiência Respiratória/terapia , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Pneumonia/complicações , Pneumonia/fisiopatologia , Valor Preditivo dos Testes , Insuficiência Respiratória/etiologia , Fatores de Risco , Falha de Tratamento
8.
Respir Care ; 62(5): 566-571, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28246308

RESUMO

BACKGROUND: A ventilator includes the function to measure flow velocity. We aimed to compare the predictive accuracy for re-intubation diagnosed by cough peak flow (CPF) measured by a spirometer and a ventilator. METHODS: Endotracheally intubated subjects who passed a spontaneous breathing trial were enrolled. Before extubation, CPF was measured by a spirometer and a ventilator, respectively. Re-intubation was recorded at 72 h after extubation. RESULTS: A total of 126 subjects were enrolled. Among them, 15 subjects (12%) experienced re-intubation. CPF was lower in re-intubated subjects than those without re-intubation (measured by a spirometer: 54 ± 30 L/min vs 86 ± 37 L/min, P < .001; and measured by a ventilator: 50 ± 22 L/min vs 80 ± 26 L/min, P < .001). CPF measured by a spirometer and a ventilator had similar area under the curve of receiver operating characteristic (0.79 vs 0.83, P = .26). When a CPF of 56.4 L/min was measured by a spirometer as cutoff value, the sensitivity and specificity to distinguish re-intubation was 73 and 87%, respectively. When it was measured by a ventilator, the cutoff value, sensitivity, and specificity were 56 L/min, 73%, and 85%, respectively. CONCLUSIONS: CPF measurement by a ventilator was convenient, affordable, and safe. It had a predictive accuracy for re-intubation similar to that of a spirometer.


Assuntos
Tosse/fisiopatologia , Intubação Intratraqueal/estatística & dados numéricos , Pico do Fluxo Expiratório/fisiologia , Espirometria/estatística & dados numéricos , Ventiladores Mecânicos/estatística & dados numéricos , Adulto , Extubação , Feminino , Humanos , Intubação Intratraqueal/métodos , Masculino , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Espirometria/métodos
9.
Intensive Care Med ; 43(2): 192-199, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27812731

RESUMO

PURPOSE: To develop and validate a scale using variables easily obtained at the bedside for prediction of failure of noninvasive ventilation (NIV) in hypoxemic patients. METHODS: The test cohort comprised 449 patients with hypoxemia who were receiving NIV. This cohort was used to develop a scale that considers heart rate, acidosis, consciousness, oxygenation, and respiratory rate (referred to as the HACOR scale) to predict NIV failure, defined as need for intubation after NIV intervention. The highest possible score was 25 points. To validate the scale, a separate group of 358 hypoxemic patients were enrolled in the validation cohort. RESULTS: The failure rate of NIV was 47.8 and 39.4% in the test and validation cohorts, respectively. In the test cohort, patients with NIV failure had higher HACOR scores at initiation and after 1, 12, 24, and 48 h of NIV than those with successful NIV. At 1 h of NIV the area under the receiver operating characteristic curve was 0.88, showing good predictive power for NIV failure. Using 5 points as the cutoff value, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for NIV failure were 72.6, 90.2, 87.2, 78.1, and 81.8%, respectively. These results were confirmed in the validation cohort. Moreover, the diagnostic accuracy for NIV failure exceeded 80% in subgroups classified by diagnosis, age, or disease severity and also at 1, 12, 24, and 48 h of NIV. Among patients with NIV failure with a HACOR score of >5 at 1 h of NIV, hospital mortality was lower in those who received intubation at ≤12 h of NIV than in those intubated later [58/88 (66%) vs. 138/175 (79%); p = 0.03). CONCLUSIONS: The HACOR scale variables are easily obtained at the bedside. The scale appears to be an effective way of predicting NIV failure in hypoxemic patients. Early intubation in high-risk patients may reduce hospital mortality.


Assuntos
Estado Terminal/terapia , Hipóxia/etiologia , Ventilação não Invasiva , Oxigenoterapia , Insuficiência Respiratória/diagnóstico , APACHE , Acidose/diagnóstico , Adulto , Idoso , Estudos de Coortes , Estado de Consciência/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Hipóxia/terapia , Unidades de Terapia Intensiva , Intubação/efeitos adversos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/métodos , Monitorização Fisiológica/estatística & dados numéricos , Ventilação não Invasiva/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Prospectivos , Insuficiência Respiratória/terapia , Taxa Respiratória , Estatísticas não Paramétricas , Falha de Tratamento
10.
Crit Care ; 20(1): 316, 2016 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-27716405

RESUMO

BACKGROUND: Reintubation is associated with high mortality. Identification of methods to avoid reintubation is needed. The aim of this study was to assess whether prophylactic noninvasive ventilation (NIV) would benefit patients with various cough strengths. METHODS: We prospectively enrolled 356 patients who successfully passed a spontaneous breathing trial in a respiratory intensive care unit. Before extubation, cough peak flow was measured. After extubation, attending physicians determined whether the patients would receive prophylactic NIV or conventional oxygen treatment (control group). Patients were followed up to 90 days postextubation or death, whichever came first. RESULTS: The median value of cough peak flow was 70 L/minute. Among the patients with cough peak flow ≤70 L/minute, 108 received NIV and 72 received conventional oxygen treatment. In this cohort, NIV reduced reintubation (9 % vs. 35 % at postextubation 72 h, p < 0.01; and 24 % vs. 49 % at postextubation 7 days, p < 0.01) and postextubation 90-day mortality (43 % vs. 61 %, p = 0.02) compared with the control group. Further, use of NIV was an independent protective factor for reintubation (OR = 0.19, p < 0.01 at 72 h postextubation; and OR = 0.33, p < 0.01 at 7 days postextubation) and for death at 90 days postextubation (OR = 0.40, p = 0.02). Among patients with cough peak flow >70 L/minute, 71 received NIV and 105 received conventional oxygen treatment. In this cohort, NIV did not reduce reintubation (6 % vs. 6 % at 72 h postextubation, p > 0.99; and 9 % vs. 9 % at 7 days postextubation, p > 0.99) or postextubation 90-day mortality (21 % vs. 15 %, p = 0.32) compared with the control group. Further, use of NIV was not associated with reintubation or postextubation 90-day mortality. CONCLUSION: In a planned extubated population, prophylactic NIV benefited patients with weak cough but possibly not in patients with strong cough.


Assuntos
Tosse/etiologia , Tosse/terapia , Ventilação não Invasiva/métodos , Respiração Artificial/normas , Desmame do Respirador/métodos , Idoso , Idoso de 80 Anos ou mais , Tosse/classificação , Feminino , Humanos , Unidades de Terapia Intensiva/organização & administração , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ventilação não Invasiva/normas , Pico do Fluxo Expiratório/fisiologia , Pneumonia/complicações , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/complicações , Respiração Artificial/efeitos adversos , Estatísticas não Paramétricas
11.
Respir Care ; 61(3): 277-84, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26715769

RESUMO

BACKGROUND: Noninvasive ventilation (NIV) intolerance is one reason for NIV failure. However, the characteristics, predictors, and outcomes of NIV intolerance are unclear. METHODS: A prospective observational study was performed in the respiratory intensive care unit of a teaching hospital. Subjects with acute respiratory failure who used NIV were enrolled. Initially, continuous use of NIV was encouraged. However, if the subject could not tolerate NIV, it was used intermittently. NIV intolerance was defined as termination of NIV due to subject refusal to receive it because of discomfort, even after intermittent use was attempted. RESULTS: A total of 961 subjects were enrolled in the study. Of these, 50 subjects (5.2%) experienced NIV intolerance after a median 2.4 h of NIV support. Age (OR = 0.98, 95% CI 0.963-0.996) and heart rate (OR = 1.02, 95% CI 1.006-1.030) measured before NIV were 2 independent risk factors of NIV intolerance. After 1-2 h of NIV, independent risk factors of NIV intolerance were heart rate (OR = 1.03, 95% CI 1.016-1.044) and breathing frequency (OR = 1.06, 95% CI 1.027-1.099). Intolerant subjects had no improvement in mean arterial pressure, heart rate, or breathing frequency after the NIV intervention. Moreover, intolerant subjects had a higher intubation rate (44.0% vs 25.8%, P = .008) and higher mortality (34.0% vs 22.4%, P = .08). The three most common complaints were that NIV worsened subjects' distress (46%), that NIV resulted in dyspnea (26%), and that the flow or pressure of NIV was too strong to bear (16%). CONCLUSIONS: NIV intolerance worsened subjects' outcomes. Younger subjects with a high heart rate and breathing frequency may be more likely to experience NIV intolerance.


Assuntos
Ventilação não Invasiva/efeitos adversos , Insuficiência Respiratória/terapia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Frequência Cardíaca , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Respiração , Insuficiência Respiratória/fisiopatologia , Fatores de Risco , Falha de Tratamento
12.
Integr Biol (Camb) ; 6(12): 1141-52, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25222482

RESUMO

The regulation of gene expression by microRNAs (miRNAs) is complex due to a number of variables involved. The potential for one miRNA to target many genes, the presence of multiple miRNA response elements (MREs) in one mRNA molecule and the interplay between RNAs that share common MREs each add a layer of complexity to the process; making it difficult to determine how regulation of gene expression by miRNAs works within the context of the system as a whole. In this study, we used luciferase report vectors inserted with different 3'UTR fragments as probes to detect the repressive effect of the miRNA pool on gene expression and uncovered some essential characteristics of gene regulation mediated by the miRNA pool, such as the nonlinear correlative relationship between the regulatory potential of a miRNA pool and the number of potential MREs, the buffering effect and the saturating effect of the miRNA pool, and the restrictive effect caused by the density of MREs. Through expressing gradient concentration of 3'UTR fragments, we indirectly detected the regulatory potential of the competing endogenous RNA (ceRNA) pool and analysed its effect on the regulatory potential of the miRNA pool. Our results provide some new insights into miRNA pool mediated gene regulation.


Assuntos
Regiões 3' não Traduzidas/genética , Regulação da Expressão Gênica/genética , Pool Gênico , MicroRNAs/genética , Modelos Genéticos , Proteoma/genética , Elementos de Resposta/genética , Sequência de Bases , Humanos , Dados de Sequência Molecular
13.
BMC Syst Biol ; 6: 64, 2012 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-22691569

RESUMO

BACKGROUND: Identification of driver mutations among numerous genomic alternations remains a critical challenge to the elucidation of the underlying mechanisms of cancer. Because driver mutations by definition are associated with a greater number of cancer phenotypes compared to other mutations, we hypothesized that driver mutations could more easily be identified once the genotype-phenotype correlations are detected across tumor samples. RESULTS: In this study, we describe a novel network analysis to identify the driver mutation through integrating both cancer genomes and transcriptomes. Our method successfully identified a significant genotype-phenotype change correlation in all six solid tumor types and revealed core modules that contain both significantly enriched somatic mutations and aberrant expression changes specific to tumor development. Moreover, we found that the majority of these core modules contained well known cancer driver mutations, and that their mutated genes tended to occur at hub genes with central regulatory roles. In these mutated genes, the majority were cancer-type specific and exhibited a closer relationship within the same cancer type rather than across cancer types. The remaining mutated genes that exist in multiple cancer types led to two cancer type clusters, one cluster consisted of three neural derived or related cancer types, and the other cluster consisted of two adenoma cancer types. CONCLUSIONS: Our approach can successfully identify the candidate drivers from the core modules. Comprehensive network analysis on the core modules potentially provides critical insights into convergent cancer development in different organs.


Assuntos
Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/genética , Genômica/métodos , Neoplasias/genética , Humanos , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Filogenia
14.
PLoS One ; 7(3): e33653, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22438977

RESUMO

A considerable portion of patients with colorectal cancer have a high risk of disease recurrence after surgery. These patients can be identified by analyzing the expression profiles of signature genes in tumors. But there is no consensus on which genes should be used and the performance of specific set of signature genes varies greatly with different datasets, impeding their implementation in the routine clinical application. Instead of using individual genes, here we identified functional multi-gene modules with significant expression changes between recurrent and recurrence-free tumors, used them as the signatures for predicting colorectal cancer recurrence in multiple datasets that were collected independently and profiled on different microarray platforms. The multi-gene modules we identified have a significant enrichment of known genes and biological processes relevant to cancer development, including genes from the chemokine pathway. Most strikingly, they recruited a significant enrichment of somatic mutations found in colorectal cancer. These results confirmed the functional relevance of these modules for colorectal cancer development. Further, these functional modules from different datasets overlapped significantly. Finally, we demonstrated that, leveraging above information of these modules, our module based classifier avoided arbitrary fitting the classifier function and screening the signatures using the training data, and achieved more consistency in prognosis prediction across three independent datasets, which holds even using very small training sets of tumors.


Assuntos
Neoplasias Colorretais/genética , Recidiva Local de Neoplasia/genética , Inteligência Artificial , Neoplasias Colorretais/cirurgia , Bases de Dados Genéticas/estatística & dados numéricos , Perfilação da Expressão Gênica/estatística & dados numéricos , Humanos , Modelos Genéticos , Família Multigênica , Mutação , Prognóstico , Fatores de Risco
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