Open AccessCDKN3 mRNA as a Biomarker for Survival and Therapeutic Target in Cervical Cancer
Author(s) -
Eira Valeria Barrón,
Edgar Román-Bassaure,
Ana Laura Sánchez-Sandoval,
Ana Espinosa,
Mariano Guardado-Estrada,
Ingrid Medina,
Eligia Juárez,
Ana Alfaro,
Miriam Bermúdez,
Rubén Zamora,
Carlos García-Ruiz,
Juan Carlos Gómora,
Susana Kofman,
E. Martha Pérez-Armendáriz,
Jaime Berumen
Publication year - 2015
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0137397
Subject(s) - biology , biomarker , proportional hazards model , cervical cancer , hazard ratio , hela , cancer , oncology , cancer research , andrology , medicine , cell culture , genetics , confidence interval
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.