RESUMEN
MicroRNAs have been suggested to be signatures for predicting recurrence in breast cancer. This study aimed to identify miR-640 and miR-525-5p as relapse-associated microRNAs in systematically untreated and lymph node negative patients with primary breast cancer. GEO datasets GSE126125 and GSE103161 were analyzed to find the differential microRNAs in primary breast cancer with and without relapse. Systematically untreated patients (n = 180) with low-risk primary breast cancer were selected in this independent validation set, and 48 patients developed relapse within 5 years. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was used to detect miR-640 and miR-525-5p expressions in tumor tissues. Based on the retrieved data from GSE126125, miR-640 and miR-525-5p expressions were significantly lower in tumors from patients with relapse compared to tumors from patients without relapse, accompanying by highly predictive potential to discriminate cases with and without relapse. The decreased miR-640 and miR-525-5p expressions were revealed in dead patients as compared to alive patients. In the independent validation set, patients with low expression of miR-640 and miR-525-5p showed poor outcome as compared to those with high expression. The receiver operating characteristic (ROC) curves of miR-640 and miR-525-5p for evaluation as diagnostic markers were depicted with the area under curves (AUCs) of 0.940 and 0.886, respectively. Tumors with larger size and higher grade had lower expression of miR-640 and miR-525-5p. MiR-640, miR-525-5p and histologic grade were significant predictors of relapse-free survival (RFS). Our study validated the values of miR-640 and miR-525-5p in predicting relapse of systematically untreated and lymph node negative patients with primary breast cancer.
Asunto(s)
Neoplasias de la Mama , MicroARNs , Humanos , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/genética , Enfermedad Crónica , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proliferación CelularRESUMEN
The aim of this study was to assess the relationship between urinary Smad1 and glomerular hyperfiltration (GHF) in type 2 diabetes mellitus (T2DM), and to explore the factors related to the urinary Smad1 in T2DM. The reference value of the estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals. 30 patients with GHF, 58 patients with norm-GFR T2DM, and 24 healthy patients who served as controls were recruited. Urinary Smad1, fasting plasma glucose (FPG), fasting serum C-Peptide (C-P), hemoglobin A1C (HbA1c), cystatin C, and other chemistry laboratory parameters of T2DM participants and controls were measured. Patients with GHF had higher levels of urinary Smad1 than the control group, and those with norm-GFR. For T2DM patients with body mass index, age, and gender adjustments, urinary Smad1 was positively correlated with FPG, HbA1C, and eGFR, but negatively correlated with fasting serum C-P. Multivariate linear regression analysis demonstrated that eGFR, HbA1C, and fasting serum C-P were independently associated with urinary Smad1. High levels of urinary Smad1 were found in GHF patients with T2DM, which may be another potential mechanism of GHF in relation to diabetic nephropathy.
Asunto(s)
Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/fisiopatología , Tasa de Filtración Glomerular/fisiología , Proteína Smad1/orina , Adulto , Biomarcadores/metabolismo , Glucemia/metabolismo , Péptido C/sangre , Estudios de Casos y Controles , Estudios Transversales , Cistatina C/sangre , Complicaciones de la Diabetes/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/metabolismo , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
AIM: To assess whether glomerular hyperfiltration (GHF) could result in renal tubular damage in type 2 diabetes mellitus (T2DM) patients. METHODS: Reference value of estimated glomerular filtration rate (eGFR) was determined in 248 healthy individuals based on serum CysC levels. GHF was defined as an eGFR exceeding the sex-specific 97.5th percentile in non-diabetic individuals. In the present study, 30 with GHF, 58 with norm-GFR T2DM, and 24 healthy controls were recruited. Tubular markers, such as urinary N-acetyl-ß-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1), as well as serum and urinary neutrophil gelatinase-associated lipocalin (NGAL), were measured and compared. The correlation of these markers with eGFR was analyzed in the GHF group. RESULTS: The GHF group had higher urinary NGAL and KIM-1 levels but lower serum NGAL level than the norm-GFR and control groups. Slightly decreased serum NGAL and increased urinary NGAL levels were also noted in the norm-GFR group compared with those of the controls. There was no statistical difference in the urinary NAG values among the three groups. Correlation analysis showed that eGFR was positively related to fasting blood glucose (FBG), HbA1c, urinary NGAL, and KIM-1, but negatively with serum NGAL in the GHF group. CONCLUSION: Higher urinary tubular damage markers were found in T2DM patients with GHF than the norm-GFR and control groups, probably a direct proof that GHF is a deleterious factor for diabetic nephropathy.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Nefropatías Diabéticas/fisiopatología , Tasa de Filtración Glomerular/fisiología , Túbulos Renales/fisiopatología , Acetilglucosaminidasa/orina , Proteínas de Fase Aguda/orina , Adulto , Anciano , Biomarcadores/sangre , Biomarcadores/orina , Glucemia/metabolismo , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/orina , Femenino , Receptor Celular 1 del Virus de la Hepatitis A , Humanos , Lipocalina 2 , Lipocalinas/sangre , Lipocalinas/orina , Masculino , Glicoproteínas de Membrana/orina , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas/orina , Receptores ViralesRESUMEN
OBJECTIVE: To examine the urinary level of tissue factor (uTF) and its procoagulant activity (PCA) in patients with diabetes mellitus, and explore the relationship between uTF and renal damage in diabetes mellitus. METHODS: Eighty-six patients with type 2 diabetes mellitus were divided into 3 groups according to urine albumin excretion (UACR), namely normal albuminuria group, microalbuminuria group and macroalbuminuria group. The levels of uTF, PCA, blood urea nitrogen (BUN), serum creatinine (CRE), serum cystatin C (CYSC), glycohemoglobin A1c (HbA1c), and high-sensitivity C-reactive protein (hs-CRP) were measured in all the patients and 21 healthy controls. RESULTS: Compared with normal control, the diabetic patients showed significantly increased levels of uTF and PCA. The urinary TF-PCA was positively correlated to BUN, CYSC, CRE, UACR, fasting glucose and hs-CRP, but not to uTF; only hs-CRP, UACR were positively correlated to uTF. CONCLUSION: uTF is probably implicated in the development and progression of diabetic nephropathy.