title: Mitosis is a source of potential markers for screening and survival and therapeutic targets in cervical cancer.
abstract: 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.
authors: Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México City, Mexico.
authors: Ana María
authors: AM
authors: Espinosa
authors: Ana
authors: A
authors: Alfaro
authors: Edgar
authors: E
authors: Roman-Basaure
authors: Mariano
authors: M
authors: Guardado-Estrada
authors: Ícela
authors: Í
authors: Palma
authors: Cyntia
authors: C
authors: Serralde
authors: Ingrid
authors: I
authors: Medina
authors: Eligia
authors: E
authors: Juárez
authors: Miriam
authors: M
authors: Bermúdez
authors: Edna
authors: E
authors: Márquez
authors: Manuel
authors: M
authors: Borges-Ibáñez
authors: Sergio
authors: S
authors: Muñoz-Cortez
authors: Avissai
authors: A
authors: Alcántara-Vázquez
authors: Patricia
authors: P
authors: Alonso
authors: José
authors: J
authors: Curiel-Valdez
authors: Susana
authors: S
authors: Kofman
authors: Nicolas
authors: N
authors: Villegas
authors: Jaime
authors: J
authors: Berumen
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*; D002584:Cervix Uteri / Q000378:metabolism; D055088:Early Detection of Cancer; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics*; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*; D055815:Young Adult; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis / Q000235:genetics / Q000401:mortality*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger