RESUMEN
BACKGROUND & AIMS: The discovery of effective and reliable biomarkers to detect hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC) at an early stage may improve the survival of HCC. The aim of this study was to establish serum microRNA (miRNA) profiles as diagnostic biomarkers for HBV-positive HCC. METHODS: We used deep sequencing to screen serum miRNAs in a discovery cohort (n=100). Quantitative polymerase chain reaction (qPCR) assays were then applied to evaluate the expression of selected miRNAs. A diagnostic 2-miRNA panel was established by a logistic regression model using a training cohort (n=182). The predicted probability of being detected as HCC was used to construct the receiver operating characteristic (ROC) curve. Area under the ROC curve (AUC) was used to assess the diagnostic performance of the selected miRNA panel. RESULTS: The predicted probability of being detected as HCC by the 2-miRNA panel was calculated by: logit P=-2.988 + 1.299 × miR-27b-3p + 1.245 × miR-192-5p. These results were further confirmed in a validation cohort (n=246).The miRNA panel provided a high diagnostic accuracy of HCC (AUC=0.842, P<.0001 for training set; AUC=0.836, P<.0001 for validation set respectively). In addition, the miRNA panel showed better prediction of HCC diagnosis than did alpha-foetoprotein (AFP). The miRNA panel also differentiated HCC from healthy (AUC=0.823, P<.0001), and cirrhosis patients (AUC=0.859, P<.0001) respectively. CONCLUSIONS: Differentially expressed serum miRNAs may have considerable clinical value in HCC diagnosis, and be particularly helpful for AFP-negative HCC.
Asunto(s)
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , MicroARNs/sangre , Adulto , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/virología , Estudios de Casos y Controles , China , Femenino , Perfilación de la Expresión Génica , Virus de la Hepatitis B , Hepatitis B Crónica/complicaciones , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/virología , Modelos Logísticos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Curva ROCRESUMEN
To establish serum microRNA profiles as prognostic biomarkers in hepatocellular carcinoma patients (HCCs), we used deep sequencing to screen serum microRNAs in a discovery set .Twelve up-regulated serum miRNAs were selected for qPCR analysis in a training set. MiR-192-5p and miR-29a-3p were identified and associated with HCC prognosis. HCCs with high concentrations of miR-192-5p and miR-29a-3p had poorer overall survival (OS) and progression-free survival (PFS) than those with low concentrations. We calculated a prognostic index (PI) score and classified patients into low-, medium- and high-risk groups. OS and PFS among the 3 groups from the training set were significantly different (all P < 0.05). PI (PIOS, PIPFS) score was the only independent prognostic predictor for OS and PFS of HCCs in the training set. These results were further confirmed in a validation set. In conclusion, differentially expressed serum miRNAs can be helpful for predicting survival in HCCs.
Asunto(s)
Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , MicroARNs/sangre , Adulto , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/virología , Supervivencia sin Enfermedad , Femenino , Hepatitis B/complicaciones , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/virología , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Sensibilidad y EspecificidadRESUMEN
BACKGROUND & OBJECTIVE: Platelet-derived growth factor receptor-alpha (PDGFRalpha) and -beta (PDGFRbeta) play important roles in the invasion and metastasis of solid tumors. However, their correlations to colorectal cancer have seldom been reported. This study was to detect the expression of PDGFRalpha and PDGFRbeta in colorectal cancer, and investigate their clinical significance. METHODS: The expression of PDGFRalpha and PDGFRbeta in 122 specimens of colorectal cancer and 17 specimens of normal colorectal tissues was detected by SABC immunohistochemistry. The correlations of their expression to the clinicopathologic characteristics and prognosis of the colorectal cancer patients were analyzed. RESULTS: The high expression rates of PDGFRalpha and PDGFRbeta were 68.8% and 65.6% in colorectal cancer, but no high expression was found in normal colorectal tissues. PDGFRalpha expression was positively correlated to PDGFRbeta expression in colorectal cancer (r=0.416, P<0.001). The expression of PDGFRalpha was positively correlated to the stage of primary lesion, regional lymph node metastasis, distant metastasis and Dukes'stage. The high expression rate of PDGFRbeta was significantly higher in Dukes'C and D tumors than in Dukes'A and B tumors (73.8% vs. 56.1%, P=0.040). The 3-year overall and progression-free survival rates were significantly lower in the patients with high PDGFRalpha expression than in those with low PDGFRalpha expression (61.5% vs. 72.1%, 43.2% vs. 72.8%, P<0.05); the 3-year progression-free survival rate was significantly lower in PDGFRalpha-positive patients than in PDGFRalpha-negative patients (47.3% vs. 72.1%, P<0.05). On multivariate analysis, both PDGFRalpha and PDGFRbeta were not independent prognostic factors of colorectal cancer. CONCLUSIONS: PDGFRalpha and PDGFRbeta are overexpressed in colorectal cancer, and are related with the progression of colorectal cancer. Both PDGFRalpha and PDGFRbeta are not independent prognostic factors of colorectal cancer.