title: CDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer.
abstract: 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.
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México; Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.
authors.forename: Eira Valeria
authors.initials: EV
authors.lastname: Barrón
authors.affiliation: Servicio de Oncología, Hospital General de México, México City, México.
authors.forename: Edgar
authors.initials: E
authors.lastname: Roman-Bassaure
authors.affiliation: Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, México.
authors.forename: Ana Laura
authors.initials: AL
authors.lastname: Sánchez-Sandoval
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Espinosa
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México.
authors.forename: Mariano
authors.initials: M
authors.lastname: Guardado-Estrada
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Medina
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México.
authors.forename: Eligia
authors.initials: E
authors.lastname: Juárez
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México.
authors.forename: Ana
authors.initials: A
authors.lastname: Alfaro
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México.
authors.forename: Miriam
authors.initials: M
authors.lastname: Bermúdez
authors.affiliation: Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, México City, México; Laboratorio de Biología Molecular, Asociación para Evitar la Ceguera en México Hospital Dr. Luis Sánchez-Bulnes, México City, México.
authors.forename: Rubén
authors.initials: R
authors.lastname: Zamora
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México.
authors.forename: Carlos
authors.initials: C
authors.lastname: García-Ruiz
authors.affiliation: Departamento de Neuropatología Molecular, División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, México.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Gomora
authors.affiliation: Servicio de Genética, Hospital General de México/Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.
authors.forename: Susana
authors.initials: S
authors.lastname: Kofman
authors.affiliation: Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.
authors.forename: E Martha
authors.initials: EM
authors.lastname: Pérez-Armendariz
authors.affiliation: Unidad de Medicina Genómica, Facultad de Medicina, Universidad Nacional Autónoma de México/ Hospital General de México, México City, México; Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, México.
authors.forename: Jaime
authors.initials: J
authors.lastname: Berumen
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics*; D063646:Carcinogenesis; D002465:Cell Movement; D049109:Cell Proliferation; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics* / Q000378:metabolism*; D015536:Down-Regulation; D054637:Dual-Specificity Phosphatases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D027383:Papillomaviridae / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D016019:Survival Analysis; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C084429:CDKN3 protein, human; D054637:Dual-Specificity Phosphatases