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Valeria Barron, Eira; Roman-Bassaure, Edgar; Laura Sanchez-Sandoval, Ana; Maria Espinosa, Ana; Guardado-Estrada, Mariano; Medina, Ingrid; Juarez, Eligia; Alfaro, Ana; Bermudez, Miriam; Zamora, Ruben; Garcia-Ruiz, Carlos; Carlos Gomora, Juan; Kofman, Susana; Martha Perez-Armendariz, E; Berumen, Jaime (2015)

CDKN3 MRNA AS A BIOMARKER FOR SURVIVAL AND THERAPEUTIC TARGET IN CERVICAL CANCER

PLoS ONE 10(9):
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The cyclin-dependent kinase inhibitor 3 (CDKN3) gene, involved in mitosis, is upregulated in cervical cancer (CC). We investigated CDKN3 mRNA as a survival biomarker and potential therapeutic target for CC. CDKN3 mRNA was measured in 134 CC and 25 controls by quantitative PCR. A 5-year survival study was conducted in 121 of these CC patients. Furthermore, CDKN3-specific siRNAs were used to investigate whether CDKN3 is involved in proliferation, migration, and invasion in CC-derived cell lines (SiHa, CaSki, HeLa). CDKN3 mRNA was on average 6.4-fold higher in tumors than in controls (p = 8 x 10-6, Mann-Whitney). A total of 68.2% of CC patients over expressing CDKN3 gene (fold change ≥ 17) died within two years of diagnosis, independent of the clinical stage and HPV type (Hazard Ratio = 5.0, 95% CI: 2.5-10, p = 3.3 x 10-6, Cox proportional-hazards regression). In contrast, only 19.2% of the patients with lower CDKN3 expression died in the same period. In vitro inactivation of CDKN3 decreased cell proliferation on average 67%, although it had no effect on cell migration and invasion. CDKN3 mRNA may be a good survival biomarker and potential therapeutic target in CC.