Mitosis Is a Source of Potential Markers for Screening and Survival and Therapeutic Targets in Cervical Cancer
Por:
Espinosa A.M., Alfaro A., Roman-Basaure E., Guardado-Estrada M., Palma Í., Serralde C., Medina I., Juárez E., Bermúdez M., Márquez E., Borges-Ibáñez M., Munoz-Cortez, S, Alcántara-Vázquez A., Alonso P., Curiel-Valdez J., Kofman S., Villegas N., Berumen J.
Publicada:
6 feb 2013
Resumen:
The effect of preventive human papillomavirus (HPV) vaccination on the
reduction of the cervical cancer (CC) burden will not be known for 30
years. Therefore, it's still necessary to improve the procedures for CC
screening and treatment. The objective of this study was to identify and
characterize cellular targets that could be considered potential markers
for screening or therapeutic targets. A pyramidal strategy was used.
Initially the expression of 8,638 genes was compared between 43
HPV16-positive CCs and 12 healthy cervical epitheliums using
microarrays. A total of 997 genes were deregulated, and 21 genes that
showed the greatest deregulation were validated using qRT-PCR. The 6
most upregulated genes (CCNB2, CDC20, PRC1, SYCP2, NUSAP1, CDKN3) belong
to the mitosis pathway. They were further explored in 29 low-grade
cervical intraepithelial neoplasias (CIN1) and 21 high-grade CIN
(CIN2/3) to investigate whether they could differentiate CC and CIN2/3
(CIN2+) from CIN1 and controls. CCNB2, PRC1, and SYCP2 were mostly
associated with CC and CDC20, NUSAP1, and CDKN3 were also associated
with CIN2/3. The sensitivity and specificity of CDKN3 and NUSAP1 to
detect CIN2+ was approximately 90%. The proteins encoded by all 6 genes
were shown upregulated in CC by immunohistochemistry. The association of
these markers with survival was investigated in 42 CC patients followed
up for at least 42 months. Only CDKN3 was associated with poor survival
and it was independent from clinical stage (HR = 5.9, 95% CI =
1.4-23.8, p = 0.01). CDKN3 and NUSAP1 may be potential targets for the
development of screening methods. Nevertheless, further studies with
larger samples are needed to define the optimal sensitivity and
specificity. Inhibition of mitosis is a well-known strategy to combat
cancers. Therefore, CDKN3 may be not only a screening and survival
marker but a potential therapeutic target in CC. However, whether it's
indispensable for tumor growth remains to be demonstrated.
Filiaciones:
Espinosa A.M.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 04510, DF, Mexico
Alfaro A.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 04510, DF, Mexico
Roman-Basaure E.:
Servicio de Oncología, Hospital General de México, México City, Mexico
Guardado-Estrada M.:
Unidad de Medicina Genómica, Hospital General de México, México City, Mexico
Palma Í.:
Escuela Superior de Medicina, Instituto Politécnico Nacional, México City, Mexico
Serralde C.:
Unidad de Medicina Genómica, Hospital General de México, México City, Mexico
Medina I.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 04510, DF, Mexico
Juárez E.:
Unidad de Medicina Genómica, Hospital General de México, México City, Mexico
Bermúdez M.:
Unidad de Medicina Genómica, Hospital General de México, México City, Mexico
Márquez E.:
Univ Nacl Autonoma Mexico, Inst Invest Matemat Aplicadas, Mexico City 04510, DF, Mexico
Borges-Ibáñez M.:
Servicio de Ginecobstetricia, Hospital General de México, México City, Mexico
Alcántara-Vázquez A.:
Servicio de Patología, Hospital General de México, México City, Mexico
Alonso P.:
Servicio de Patología, Hospital General de México, México City, Mexico
Curiel-Valdez J.:
Unidad de Medicina Genómica, Hospital General de México, México City, Mexico
Kofman S.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 04510, DF, Mexico
Villegas N.:
Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del Instituto Politécnico Nacional, México City, Mexico
Berumen J.:
Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 04510, DF, Mexico
Gold
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