J Cañueto1,2, E Cardeñoso-Álvarez3, J L García-Hernández2,4, P Galindo-Villardón5, P Vicente-Galindo5, J L Vicente-Villardón5, D Alonso-López2,4,6, J De Las Rivas2,4,6, J Valero4, E Moyano-Sanz1, E Fernández-López1,2, J H Mao7, A Castellanos-Martín2,4, C Román-Curto1,2, J Pérez-Losada2,4. 1. Departamento de Dermatología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. 2. Instituto de Investigación Biomédica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Paseo de San Vicente, 58-182, 37007, Salamanca, Spain. 3. Departamento de Dermatología, Hospital Virgen de la Concha, Avenida de Requejo, Zamora, Spain. 4. 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. 5. Departamento de Estadística, Universidad de Salamanca, Campus Miguel de Unamuno, s.n. 37007, Salamanca, Spain. 6. Unidad de Bioinformática, CIC-IBMCC, Salamanca, 37007, Spain. 7. Life Sciences Division, Lawrence Berkeley National Laboratory, University of California, Berkeley, CA, 94720, U.S.A.
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. OBJECTIVES: 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.
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. OBJECTIVES: We aimed to identify the expression pattern of microRNAs (miRNAs or miRs) at different stages of skin cancer progression in a panel of murineskin 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 humantumours. 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 murineskin 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: George Adrian Calin; Cinzia Sevignani; Calin Dan Dumitru; Terry Hyslop; Evan Noch; Sai Yendamuri; Masayoshi Shimizu; Sashi Rattan; Florencia Bullrich; Massimo Negrini; Carlo M Croce Journal: Proc Natl Acad Sci U S A Date: 2004-02-18 Impact factor: 11.205
Authors: A M Lena; R Shalom-Feuerstein; P Rivetti di Val Cervo; D Aberdam; R A Knight; G Melino; E Candi Journal: Cell Death Differ Date: 2008-05-16 Impact factor: 15.828
Authors: Christine E Wong; Jennifer S Yu; David A Quigley; Minh D To; Kuang-Yu Jen; Phillips Y Huang; Reyno Del Rosario; Allan Balmain Journal: Genes Dev Date: 2013-03-15 Impact factor: 11.361
Authors: Paola Tucci; Massimiliano Agostini; Francesca Grespi; Elke K Markert; Alessandro Terrinoni; Karen H Vousden; Patricia A J Muller; Volker Dötsch; Sebastian Kehrloesser; Berna S Sayan; Giuseppe Giaccone; Scott W Lowe; Nozomi Takahashi; Peter Vandenabeele; Richard A Knight; Arnold J Levine; Gerry Melino Journal: Proc Natl Acad Sci U S A Date: 2012-09-04 Impact factor: 11.205