RESUMEN
A new algorithm has been developed for bioinformatics search of putative serum markers of cancer, which includes: 1) identification of microRNAs that are most often and most significantly overexpressed in tumors; 2) selection of mRNA targets regulated by microRNAs; 3) identification of mRNA targets encoding secreted proteins; 4) comparative analysis of mRNA transcription levels in normal and tumor tissues. Application of the algorithm led to discovery of seven putative serum markers of colon cancer: ADAMTS14, ANGPT2, CCL7, DEFA5, MMP11, MMP14, and PLAU. Experiments demonstrated that production of two out of seven proteins (MMP14 and DEFA5) is significantly increased in colon tumors vs. normal samples.
Asunto(s)
Biomarcadores de Tumor/sangre , Biología Computacional/métodos , MicroARNs/genética , Neoplasias/sangre , Algoritmos , Biomarcadores de Tumor/genética , Bases de Datos Genéticas , Defensinas/sangre , Defensinas/genética , Perfilación de la Expresión Génica , Humanos , Metaloproteinasa 14 de la Matriz/sangre , Metaloproteinasa 14 de la Matriz/genética , Neoplasias/diagnósticoRESUMEN
Modification of 2D analysis protocol was developed, based on preliminary removal of major cellular proteins by extraction with buffer saline and elimination of high molecular weight proteins by gel filtration. This approach allowed identification of 12 proteins with increased expression levels in tumors versus normal tissues. Increase in expression levels of the eight proteins in colon tumors was discovered for the first time. We performed comparison of marker search efficiency by 2D analysis and SAGE in a control panel of 19 putative colon cancer markers, discovered by us previously and at the same time independently identified by other authors. Results of 2D analysis of control panel completely coincided with published data, as compared to search in SAGE database, which allowed identification of only one third of markers.
