2026-09-15T18:18:30Zhttps://gredos.usal.es/oai/request
oai:gredos.usal.es:10366/1610072026-01-15T20:40:36Zcom_10366_3974com_10366_3947com_10366_3946com_10366_3823col_10366_3975
Gestión del Repositorio Documental de la Universidad de Salamanca author Rodríguez Carreño, Alba author Corchete Sánchez, Luis Antonio author Alcázar Montero, José Antonio author Montero González, Juan Carlos author Rodríguez González, Marta author Chinchilla-Tábora, Luís Miguel author Vidal Tocino, María del Rosario author Moyano, Carlos author Muñoz-Bravo, Saray author Sayagués Manzano, José María author Abad Hernández, María Mar 2024-12-10T12:16:58Z 2024-12-10T12:16:58Z 2022 Rodriguez, A., Corchete, L. A., Alcazar, J. A., Montero, J. C., Rodriguez, M., Chinchilla-Tábora, L. M., Vidal Tocino, R., Moyano, C., Muñoz-Bravo, S., Sayagués, J. M., y Abad, M. (2022). Dysregulated expression of three genes in colorectal cancer stratifies patients into three risk groups. Cancers, 14(17), 4076. https://doi.org/10.3390/cancers14174076 http://hdl.handle.net/10366/161007 10.3390/cancers14174076 2072-6694 [EN]Despite advances in recent years in the study of the molecular profile of sporadic colorectal cancer (sCRC), the specific genetic events that lead to increased aggressiveness or the development of the metastatic process of tumours are not yet clear. In previous studies of the gene expression profile (GEP) using a high-density array (50,000 genes and 6000 miRNAs in a single assay) in sCRC tumours, we identified a 28-gene signature that was found to be associated with an adverse prognostic value for predicting patient survival. Here, we analyse the differential expression of these 28 genes for their possible association with tumour local aggressiveness and metastatic processes in 66 consecutive sCRC patients, followed for >5 years, using the NanoString nCounter platform. The global transcription profile (expression levels of the 28 genes studied simultaneously) allowed us to discriminate between sCRC tumours and nontumoral colonic tissues. Analysis of the biological and functional significance of the dysregulated GEPs observed in our sCRC tumours revealed 31 significantly altered canonical pathways. Among the most commonly altered pathways, we observed the increased expression of genes involved in signalling pathways and cellular processes, such as the PI3K-Akt pathway, the interaction with the extracellular matrix (ECM), and other functions related to cell signalling processes (SRPX2). From a prognostic viewpoint, the altered expression of BST2 and SRPX2 genes were the only independent variables predicting for disease-free survival (DFS). In addition to the pT stage at diagnosis, dysregulated transcripts of ADH1B, BST2, and FER1L4 genes showed a prognostic impact on OS in the multivariate analysis. Based on the altered expression of these three genes, a scoring system was built to stratify patients into low-, intermediate-, and high-risk groups with significantly different 5-year OS rates: 91%, 83%, and 52%, respectively. The prognostic impact was validated in two independent series of sCRC patients from the public GEO database (n = 562 patients). In summary, we show a strong association between the altered expression of three genes and the clinical outcome of sCRC patients, making them potential markers of suitability for adjuvant therapy after complete tumour resection. Additional prospective studies in larger series of patients are required to confirm the clinical utility of the newly identified biomarkers because the number of patients analysed remains small. eng Atribución 4.0 Internacional Colorectal cancer Tumour aggressiveness GEP Dysregulated Expression of Three Genes in Colorectal Cancer Stratifies Patients into Three Risk Groups info:eu-repo/semantics/article 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 URL https://gredos.usal.es/bitstream/10366/161007/1/dysregulated....pdf File MD5 a48f99e900e9bcfdbd5f92b6859a2ceb 3483716 application/pdf dysregulated....pdf URL https://gredos.usal.es/bitstream/10366/161007/4/dysregulated....pdf.txt File MD5 d69a133669c2475fcb4db4ec07a72412 54106 text/plain dysregulated....pdf.txt