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1.
Cell Physiol Biochem ; 44(3): 1213-1223, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29179219

RESUMO

BACKGROUND/AIMS: Acute rejection (AR) is a major complication post renal transplantation, with no widely-accepted non-invasive biomarker. This study aimed to explore the expression profiles of long non-coding RNAs (lncRNAs) in the peripheral blood (PB) of renal transplant recipients and their potential diagnostic values. METHODS: The genome-wide lncRNA expression profiles were analyzed in 150 PB samples from pediatric and adult renal transplant (PRTx and ARTx) cohorts. The diagnostic performance of differentially expressed lncRNA was determined using receiver operator characteristic curve, with area under the curve (AUC) and 95% confidential interval (CI). Finally, a risk score was constructed with logistical regression model. RESULTS: A total of 162 lncRNAs were found differentially expressed in PRTx cohort, while 163 in ARTx cohort. Among these identified lncRNAs, 23 deregulated accordingly in both cohorts, and could distinguish AR recipients from those without AR. Finally, a risk score with two most significant lncRNAs (AF264622 and AB209021) was generated and exhibited excellent diagnostic performance in both PRTx (AUC:0.829, 95% CI:0.735-0.922) and ARTx cohorts (AUC: 0.889, 95% CI: 0.817-0.960). CONCLUSION: A molecular signature of two lncRNAs in PB could serve as a novel non-invasive biomarker for the diagnosis of AR in both pediatric and adult renal transplant recipients.


Assuntos
Rejeição de Enxerto/patologia , Transplante de Rim , RNA Longo não Codificante/sangue , Doença Aguda , Área Sob a Curva , Biomarcadores/sangue , Estudos de Coortes , Rejeição de Enxerto/genética , Rejeição de Enxerto/metabolismo , Humanos , Curva ROC , Transcriptoma , Transplante Homólogo
2.
J Cancer ; 8(13): 2643-2652, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28900502

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is the most prevalent histologic subtype of kidney cancers in adults, which could be divided into two distinct subgroups according to the BRCA1 associated protein-1 (BAP1) mutation status. In the current study, we comprehensively analyzed the genome-wide microRNA (miRNA) expression profiles in ccRCC, with the aim to identify the differentially expressed miRNAs between BAP1 mutant and wild-type tumors, and generate a BAP1 mutation-specific miRNA signature for ccRCC patients with wild-type BAP1. Methods: The BAP1 mutation status and miRNA profiles in BAP1 mutant and wild-type tumors were analyzed. Subsequently, the association of the differentially expressed miRNAs with patient survival was examined, and a BAP1 mutation-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate and multivariate Cox regression analyses. Finally, the bioinformatics methods were adopted for the target prediction of selected miRNAs and functional annotation analyses. Results: A total of 350 treatment-naïve primary ccRCC patients were selected from The Cancer Genome Atlas project, among which 35 (10.0%) subjects carried mutant BAP1 and had a shorter overall survival (OS) time. Furthermore, 33 miRNAs were found to be differentially expressed between BAP1 mutant and wild-type tumors, among which 11 (miR-149, miR-29b-2, miR-182, miR-183, miR-21, miR-365-2, miR-671, miR-365-1, miR-10b, miR-139, and miR-181a-2) were significantly associated with OS in ccRCC patients with wild-type BAP1. Finally, a BAP1 mutation-specific miRNA signature consisting of 11 miRNAs was generated and validated as an independent prognostic parameter. Conclusions: In summary, our study identified a total of 33 miRNAs differentially expressed between BAP1 mutant and wild-type tumors, and generated a BAP1 mutation-specific miRNA signature including eleven miRNAs, which could serve as a novel prognostic biomarker for ccRCC patients with wild-type BAP1.

3.
Int J Clin Exp Pathol ; 8(2): 1128-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25972999

RESUMO

BACKGROUND: Ischemic preconditioning (IPC) could protect against subsequent renal ischemia reperfusion injury (IRI). However, the mechanisms underlying IPC remain far from complete. Hence, we explored the effects of IPC on the renal and systemic hemodynamic changes, renal function and morphology, as well the involvement of endothelial and inducible nitric oxide synthase (eNOS/iNOS), and nitric oxide (NO). METHODS: Male Sprague-Dawley rats were randomly divided into five groups after right-side nephrectomy: Sham group (surgery without vascular clamping); IRI group (the left renal artery was clamped for 45 min); IPC group (pretreated with 15 min of ischemia and 10 min of reperfusion); IPC + vehicle group (administrated with 0.9% saline 5 min before IPC); and IPC + N(G)-nitro-L-arginine methylester (L-NAME) group (pretreated with L-NAME 5 min prior to IPC). The renal and systemic hemodynamic parameters, renal function and morphology, as well as eNOS, iNOS, and NO expression levels in the kidneys were measured at the indicated time points after reperfusion. RESULTS: IPC rats exhibited significant improvements in renal function, morphology, and renal artery blood flow (RABF), without obvious influence on the systemic hemodynamics and renal vein blood flow. Increased eNOS, iNOS, and NO expression levels were detected in the kidneys of IPC rats 24 h after reperfusion. Furthermore, the beneficial effects were fully abolished by the administration of L-NAME. CONCLUSIONS: The results suggest that IPC contributes to early restoration of RABF, probably through eNOS/iNOS-mediated NO production, thereby alleviating the renal dysfunction and histological damage caused by IRI.


Assuntos
Precondicionamento Isquêmico/métodos , Rim/irrigação sanguínea , Traumatismo por Reperfusão/fisiopatologia , Animais , Hemodinâmica/efeitos dos fármacos , Hemodinâmica/fisiologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo
4.
Medicine (Baltimore) ; 94(16): e767, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25906110

RESUMO

Papillary renal cell carcinoma (pRCC) is the second most prevalent subtype of kidney cancers. In the current study, we analyzed the global microRNA (miRNA) expression profiles in pRCC, with the aim to evaluate the relationship of miRNA expression with the progression and prognosis of pRCC.A total of 163 treatment-naïve primary pRCC patients were identified from the Cancer Genome Atlas dataset and included in this retrospective observational study. The miRNA expression profiles were graded by tumor-node-metastasis information, and compared between histologic subtypes. Furthermore, the training-validation approach was applied to identify miRNAs of prognostic values, with the aid of Kaplan-Meier survival, and univariate and multivariate Cox regression analyses. Finally, the online DAVID (Database for Annotation, Visualization, and Integrated Discover) program was applied for the pathway enrichment analysis with the target genes of prognosis-associated miRNAs, which were predicted by 3 computational algorithms (PicTar, TargetScan, and Miranda).In the progression-related miRNA profiles, 26 miRNAs were selected for pathologic stage, 28 for pathologic T, 16 for lymph node status, 3 for metastasis status, and 32 for histologic types, respectively. In the training stage, the expression levels of 12 miRNAs (mir-134, mir-379, mir-127, mir-452, mir-199a, mir-200c, mir-141, mir-3074, mir-1468, mir-181c, mir-1180, and mir-34a) were significantly associated with patient survival, whereas mir-200c, mir-127, mir-34a, and mir-181c were identified by multivariate Cox regression analyses as potential independent prognostic factors in pRCC. Subsequently, mir-200c, mir-127, and mir-34a were confirmed to be significantly correlated with patient survival in the validation stage. Finally, target gene prediction analysis identified a total of 113 target genes for mir-200c, 37 for mir-127, and 180 for mir-34a, which further generated 15 molecular pathways.Our results identified the specific miRNAs associated with the progression and aggressiveness of pRCC, and 3 miRNAs (mir-200c, mir-127, and mir-34a) as promising prognostic factors of pRCC.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , MicroRNAs/biossíntese , Fatores Etários , Idoso , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores Sexuais
5.
Biomed Pharmacother ; 69: 29-33, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25661334

RESUMO

PURPOSE: Current evidence suggests that preconditioning with erythropoietin (EPO) can protect against ischemia reperfusion injury in rodents. However, randomized controlled trials (RCTs) assessing the efficacy and safety of high-dose EPO in kidney transplantation have yielded inconclusive results. Herein, we performed a meta-analysis of RCTs to assess whether the administration of high-dose EPO can improve graft function and the potential adverse events. METHODS: Relevant RCT studies that investigated high-dose EPO on graft function after kidney transplantation were comprehensively searched in Pubmed, Embase, and Cochrane Library until July 10, 2014. All statistical analyses were performed using Review Manager 5.0 and STATA 12.0. RESULTS: A total of 4 RCTs involving 356 patients were identified. Comprehensively, a trend of reduction in the incidence of delayed graft function could be observed in the EPO group (EPO vs. placebo groups: RR=0.88); however, the result did not reach the significance level (95% CI, 0.72-1.08; P=0.21). Furthermore, no significant difference in the incidences of adverse events was observed between the two groups. CONCLUSIONS: The current meta-analysis indicates that the administration of high-dose EPO is, to some extent, prone to protect kidney function without increasing the susceptibility to adverse events.


Assuntos
Eritropoetina/administração & dosagem , Eritropoetina/uso terapêutico , Transplante de Rim , Ensaios Clínicos Controlados Aleatórios como Assunto , Intervalos de Confiança , Relação Dose-Resposta a Droga , Eritropoetina/efeitos adversos , Humanos , Transplante de Rim/efeitos adversos , Viés de Publicação
6.
J Cancer Res Clin Oncol ; 141(7): 1291-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25633718

RESUMO

PURPOSE: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancers in adults, and microRNAs (miRNAs) differentially expressed in ccRCC tumors have been identified and proposed to predict prognosis. In the present study, we comprehensively analyzed the genome-wide miRNA expression profiles in ccRCC, with the aim to generate a tumor-specific miRNA signature of prognostic values. METHODS: The miRNA profiles in tumor and the adjacent normal tissue were analyzed, and the association of the differentially expressed miRNAs with patient survival was examined with univariate Cox regression analysis. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate, and multivariate Cox regression analyses. RESULTS: A total of 147 miRNAs were found differentially expressed between tumor and matched non-tumor tissues from 58 ccRCC patients. The prognostic values of these differentially expressed miRNAs were subsequently analyzed in the 411 ccRCC patients, and 22 miRNAs were found significantly correlated with patient survival. Finally, a tumor-specific miRNA signature of 22 miRNAs was generated and validated as an independent prognostic parameter. CONCLUSIONS: A tumor-specific miRNA signature consisting of 22 miRNAs was identified and validated as an independent prognostic factor, which could serve as a novel biomarker for ccRCC prognostication and help in predicting treatment outcome.


Assuntos
Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , MicroRNAs/genética , Transcriptoma , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/diagnóstico , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Especificidade de Órgãos/genética , Prognóstico , Análise de Sobrevida
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