RESUMO
BACKGROUND: We identified and validated novel urinary autophagy markers in diabetic kidney disease (DKD) based on bioinformatics analysis and clinical validation. PATIENTS & METHODS: We retrieved three novel autophagy genes related to DKD from public microarray databases, namely; microtubule-associated protein light chain (MAP1LC3A), WD Repeat Domain, Phosphoinositide Interacting 2 (WIPI2), and RB1-Inducible Coiled-Coil 1 (RB1CC1). Secondly we assessed the expression of the chosen autophagy transcript in urine sediment of 86 patients with DKD and 74 (age and sex matched) controls by reverse transcription quantitative real-time PCR. RESULTS: The urinary expression levels of MAP1LC3A, WIPI, RB1CC1 were significantly lower in DKD than control group (P<0.001).The receiver-operating characteristic curve (ROC) analyses that each urinary autophagy transcript showed high sensitivity and specificity for distinguishing DKD from control (MAP1LC3A, 81.4% and 81.1%; WIPI, 74.4% and 67.6%, and RB1CC1, 81.4%,70.3%, respectively). Notably, a negative correlation was found between these autophagy markers, serum creatinine and urinary albumin creatinine ratio. The sensitivity and specificity of this urinary autophagy based panel reached 90.6% and 60% in diagnosis of DKD. CONCLUSION: We identified and validated a novel diagnostic urinary autophagy based panel with high sensitivity and moderate specificity representing a vital player in the pathogenesis of DKD.
Assuntos
Proteínas de Transporte/metabolismo , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/urina , Regulação para Baixo , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Tirosina Quinases/metabolismo , RNA Mensageiro/urina , Idoso , Albuminúria/etiologia , Autofagia , Proteínas Relacionadas à Autofagia , Biomarcadores/urina , Proteínas de Transporte/genética , Estudos de Coortes , Biologia Computacional , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/fisiopatologia , Feminino , Regulação da Expressão Gênica , Humanos , Rim/metabolismo , Rim/fisiopatologia , Masculino , Proteínas de Membrana/genética , Proteínas Associadas aos Microtúbulos/genética , Pessoa de Meia-Idade , Proteínas de Ligação a Fosfato , Proteínas Tirosina Quinases/genética , RNA Mensageiro/metabolismo , Insuficiência Renal/complicações , Insuficiência Renal/diagnóstico , Insuficiência Renal/metabolismo , Insuficiência Renal/fisiopatologia , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
Gastric cancer (GC) is a global health problem and a major cause of cancer-related death with high recurrence rates ranging from 25% to 40% for GC patients staging II-IV. Unfortunately, while the majority of GC patients usually present with advanced tumor stage; there is still limited evidence-based therapeutic options. Current approach to GC management consists mainly of; endoscopy followed by, gastrectomy and chemotherapy or chemo-radiotherapy. Recent studies in GC have confirmed that it is a heterogeneous disease. Many molecular characterization studies have been performed in GC. Recent discoveries of the molecular pathways underlying the disease have opened the door to more personalized treatment and better predictable outcome. The identification of molecular markers is a useful tool for clinical managementin GC patients, assisting in diagnosis, evaluation of response to treatment and development of novel therapeutic modalities. While chemotherapeutic agents have certain physiological effects on the tumor cells, the prediction of the response is different from one type of tumor to the other. The specificity of molecular biomarkers is a principal feature driving their application in anticancer therapies. Here we are trying to focus on the role of molecular pathways of GC and well-established molecular markers that can guide the therapeutic management.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Biomarcadores Tumorais/metabolismo , Humanos , Terapia de Alvo Molecular , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMO
BACKGROUND: Long noncoding RNAs(lncRNAs) have emerged as key elements in modulating gene expression in different biological contexts. PATIENTS AND METHODS: We used quantitative real-time PCR (Qpcr) to evaluate the expression of lncRNA-UCA1 and C-JUN in serum of 70 patients with hepatocellular carcinoma (HCC), 32 patients chronic hepatitis C (CHC) and 38 healthy subjects and their correlation with different clinicopathological factors. RESULTS: The expression of lncRNA-UCA1 and C-JUN was positive in 91.4%HCC patients with strong discriminating power between HCC and healthy subjects and CHC patients as well. The median follow up period was 29 months. The survival analysis showed that both lncRNA-UCA1 and C-JUN were independent prognostic factors. Of note, we identified C-JUN expression changes consistent with the lncRNA-UCA1 target regulation. CONCLUSION: This information sheds light on the possible role of lncRNA-UCA1 and C-JUN mRNA as promising diagnostic and prognostic markers as well as potential therapeutic targets in HCC.
