title: MicroRNA (miR)-203 and miR-205 expression patterns identify subgroups of prognosis in cutaneous squamous cell carcinoma.
abstract: BACKGROUND
  Cutaneous squamous cell carcinoma (CSCC) is the second most widespread cancer in humans and its incidence is rising. These tumours can evolve as diseases of poor prognosis, and therefore it is important to identify new markers to better predict its clinical evolution.
  
  
  OBJECTIVE
  We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murine skin cancer cell lines. Owing to the increasing importance of miRNAs in the pathogenesis of cancer, we considered the possibility that miRNAs could help to define the prognosis of CSCC and aimed to evaluate the potential use of miR-203 and miR-205 as biomarkers of prognosis in human tumours.
  
  
  METHODS
  Seventy-nine human primary CSCCs were collected at the University Hospital of Salamanca in Spain. We identified differential miRNA expression patterns at different stages of CSCC progression in a well-established panel of murine skin cancer cell lines, and then selected miR-205 and miR-203 to evaluate their association with the clinical prognosis and evolution of human CSCC.
  
  
  RESULTS
  miR-205 was expressed in tumours with pathological features recognized as indicators of poor prognosis such as desmoplasia, perineural invasion and infiltrative growth pattern. miR-205 was mainly expressed in undifferentiated areas and in the invasion front, and was associated with both local recurrence and the development of general clinical events of poor evolution. miR-205 expression was an independent variable selected to predict events of poor clinical evolution using the multinomial logistic regression model described in this study. In contrast, miR-203 was mainly expressed in tumours exhibiting the characteristics associated with a good prognosis, was mainly present in well-differentiated zones, and rarely expressed in the invasion front. Therefore, the expression and associations of miR-205 and miR-203 were mostly mutually exclusive. Finally, using a logistic biplot we identified three clusters of patients with differential prognosis based on miR-203 and miR-205 expression, and pathological tumour features.
  
  
  CONCLUSIONS
  miR-205 and miR-203 tended to exhibit mutually exclusive expression patterns in human CSCC. This work highlights the utility of miR-205 and miR-203 as prognostic markers in CSCC.
authors.affiliation: Departamento de Dermatología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
authors.forename: J
authors.identifier: http://orcid.org/0000-0003-0037-7353
authors.initials: J
authors.lastname: Cañueto
authors.affiliation: Departamento de Dermatología, Hospital Virgen de la Concha, Avenida de Requejo, Zamora, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Cardeñoso-Álvarez
authors.affiliation: Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Centro de Investigación del Cáncer (CIC), Universidad de Salamanca/CSIC, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: García-Hernández
authors.affiliation: Departamento de Estadística, Universidad de Salamanca, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Galindo-Villardón
authors.affiliation: Departamento de Estadística, Universidad de Salamanca, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Vicente-Galindo
authors.affiliation: Departamento de Estadística, Universidad de Salamanca, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Vicente-Villardón
authors.affiliation: Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Centro de Investigación del Cáncer (CIC), Universidad de Salamanca/CSIC, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.|Unidad de Bioinformática, CIC-IBMCC, Salamanca, 37007, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Alonso-López
authors.affiliation: Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Centro de Investigación del Cáncer (CIC), Universidad de Salamanca/CSIC, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.|Unidad de Bioinformática, CIC-IBMCC, Salamanca, 37007, Spain.
authors.forename: J
authors.initials: J
authors.lastname: De Las Rivas
authors.affiliation: Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Centro de Investigación del Cáncer (CIC), Universidad de Salamanca/CSIC, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Valero
authors.affiliation: Departamento de Dermatología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Moyano-Sanz
authors.affiliation: Departamento de Dermatología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Fernández-López
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA, 94720, U.S.A.
authors.forename: J H
authors.initials: JH
authors.lastname: Mao
authors.affiliation: Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Centro de Investigación del Cáncer (CIC), Universidad de Salamanca/CSIC, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Castellanos-Martín
authors.affiliation: Departamento de Dermatología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Román-Curto
authors.affiliation: Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain.|Instituto de Biología Molecular y Celular del Cáncer (IBMCC), Centro de Investigación del Cáncer (CIC), Universidad de Salamanca/CSIC, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Pérez-Losada
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D018450:Disease Progression; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D060787:Neoplasm Grading; D011379:Prognosis; D012878:Skin Neoplasms / Q000175:diagnosis*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; C546703:MIRN203 microRNA, human; C534425:MIR205, human