RESUMEN
MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.
Asunto(s)
Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Línea Celular Tumoral , Cisplatino/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Pulmón/efectos de los fármacos , Neoplasias Pulmonares/sangre , Ratones Desnudos , MicroARNs/sangre , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.
Asunto(s)
Animales , Femenino , Humanos , Masculino , Ratones , Persona de Mediana Edad , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Línea Celular Tumoral , Cisplatino/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Pulmón/efectos de los fármacos , Neoplasias Pulmonares/sangre , Ratones Desnudos , MicroARNs/sangre , Pronóstico , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
Objective To inquire and compare the value of 4 proteins in the cerebrospinal fluid (CSF) for early diagnosis of Creutzfeldt-Jakob disease (CJD).Methods The CSF samples were obtained from 14 CJD patients in the early stage,t-tan,t-tan,t-tau/t-tau,S-100?,14-3-3 and 14-3-2 protein had been examined and compared with other dementia (OD) and none dementia (ND) as controls by capture assay and ELISA.Results (1)t-tan protein: the concentration in CJD ,OD and ND is 8295,300 and 161 pg/ml respectively,t-tau/t-tau ratio is 0.0092,0.2258 and 0.2471 respectively.(2) S-100? protein: the concentration in CJD,OD and ND is 1.576,0.639 and 0.239 ng/ml respectively.(3) 14-3-3 protein:the concentration in CJD,OD and ND is 40.00,2.65 and 3.10 ng/ml respectively.(4) 14-3-2 protein: the concentration in CJD,OD and ND is 48.43,14.00 and 20.50 ng/ml respectively.(5) At the cut-off point 500 pg/ml for t-tan,sensitivity for diagnosis of CJD is 84.6% and specificity is 87.6% ,t-tan has no diagnostic value to CJD.(6) At 1.626 ng/ml for S-100?,the sensitivity is 92.3% and specificity is 83.8%.(7) At 9 ng/ml for 14-3-3 protein,the sensitivity is 86.7% and specificity is 86.4%.(8) At a level of24 ng/ml for 14-3-2 protein,the sensitivity for diagnosis of CJD is 78.6% and specificity is 77.3%. Conclusion It is the CSF detection of neuroproteins that have great valuble significance in diagnosis for sporadic CJD in the early stage.