Mitosis is a source of potential markers for screening and survival and therapeutic targets in cervical cancer

Autor: Nicolás Villegas, Jose de Jesus Curiel-Valdez, Ingrid Medina, Mariano Guardado-Estrada, Cyntia Serralde, Patricia Alonso, Ana Alfaro, Manuel Borges-Ibañez, Edgar Roman-Basaure, Avissai Alcántara-Vázquez, Icela Palma, Edna Marquez, Miriam Bermúdez, Sergio Muñoz-Cortez, Ana María Espinosa, Eligia Juárez, Susana Kofman, Jaime Berumen
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Oncology
Viral Diseases
Epidemiology
Uterine Cervical Neoplasms
lcsh:Medicine
Cervix Uteri
Bioinformatics
Cervical Cancer
Papillomaviridae
lcsh:Science
Early Detection of Cancer
Oligonucleotide Array Sequence Analysis
Cervical cancer
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Genomics
Middle Aged
Real-time polymerase chain reaction
Infectious Diseases
Carcinoma
Squamous Cell
Adenocarcinoma
Medicine
Female
Cancer Screening
Research Article
Adult
medicine.medical_specialty
Human Papillomavirus Infection
Mitosis
CDC20
Biology
Cervical intraepithelial neoplasia
Real-Time Polymerase Chain Reaction
Sensitivity and Specificity
Young Adult
Internal medicine
medicine
Carcinoma
Biomarkers
Tumor
Cancer Detection and Diagnosis
Humans
Neoplasm Invasiveness
RNA
Messenger
Aged
Gene Expression Profiling
Papillomavirus Infections
lcsh:R
Cancers and Neoplasms
medicine.disease
biology.organism_classification
Uterine Cervical Dysplasia
Gene expression profiling
Biomarker Epidemiology
lcsh:Q
Neoplasm Grading
Genome Expression Analysis
Gynecological Tumors
Zdroj: PLoS ONE, Vol 8, Iss 2, p e55975 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
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