| Autor: |
Alvarez-Cubero MJ; GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Genomics Unit, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain.; Nutrition, Diet and Risk Assessment Group, Bio-Health Research Institute (Instituto de Investigación Biosanitaria ibs.GRANADA), Avenida de las Fuerzas Armadas 2, 18014 Granada, Spain.; Department of Biochemistry and Molecular Biology III, Faculty of Medicine, University of Granada, PTS Granada, 18016 Granada, Spain., Arance E; GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Genomics Unit, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain., de Santiago E; GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Genomics Unit, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain., Sanchez P; Department of Biochemistry and Molecular Biology III, Faculty of Medicine, University of Granada, PTS Granada, 18016 Granada, Spain., Sepúlveda MR; Department of Cell Biology, Faculty of Sciences, University of Granada, Avenida de la Fuente Nueva S/N CP, 18071 Granada, Spain., Marrero R; GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Genomics Unit, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain., Lorente JA; GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Genomics Unit, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain.; Department of Legal Medicine and Toxicology, Faculty of Medicine, University of Granada, PTS Granada, 18016 Granada, Spain., Gonzalez-Cabezuelo JM; Meridiem Seeds, Research and Development Department, 04710 Almería, Spain., Cuenca-Lopez S; GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Genomics Unit, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain.; Department of Biochemistry and Molecular Biology III, Faculty of Medicine, University of Granada, PTS Granada, 18016 Granada, Spain., Cozar JM; Urology Department, Virgen de las Nieves Hospital, 18014 Granada, Spain., Vazquez-Alonso F; Urology Department, Virgen de las Nieves Hospital, 18014 Granada, Spain., Martinez-Gonzalez LJ; GENYO, Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Genomics Unit, PTS Granada, Avenida de la Ilustración 114, 18016 Granada, Spain. |
| Abstrakt: |
The management and screening of prostate cancer (PC) is still the main problem in clinical practice. In this study, we investigated the role of aggressiveness genetic markers for PC stratification. We analyzed 201 plasma samples from PC patients and controls by digital PCR. For selection and validation, 26 formalin-fixed paraffin-embedded tissues, 12 fresh tissues, and 24 plasma samples were characterized by RNA-Seq, immunochemistry, immunofluorescence, Western blot, and extracellular-vesicles analyses. We identified three novel non-invasive biomarkers; all with an increased expression pattern in patients ( PCA3 : p = 0.002, S100A4 : p ≤ 0.0001 and MRC2 : p = 0.005). S100A4 presents the most informative AUC (area under the curve) (0.735). Combination of S100A4 , MRC2 , and PCA3 increases the discriminatory power between patients and controls and between different more and less aggressive stages (AUC = 0.761, p ≤ 0.0001). However, although a sensitivity of 97.47% in PCA3 and a specificity of 90.32% in S100A4 was reached, the detection signal level could be variable in some analyses owing to tumor heterogeneity. This is the first time that the role of S100A4 and MRC2 has been described in PC aggressiveness. Moreover, the combination of S100A4 , MRC2 , and PCA3 has never been described as a non-invasive biomarker for PC screening and aggressiveness. |
