DNA replication licensing factor MCM2, geminin, and Ki67 define proliferative state and are linked with survival in oral squamous cell carcinoma

被引:8
作者
Al-Hazmi, Nadia [1 ]
Alhazzazi, Turki [1 ]
Williams, Gareth [2 ]
Stoeber, Kai [2 ]
Al-Dabbagh, Raghad [3 ]
机构
[1] King Abdulaziz Univ, Fac Dent, Dept Oral Biol, Jeddah, Saudi Arabia
[2] UCL, UCL Canc Inst, Dept Pathol, London, England
[3] King Abdulaziz Univ, Dept Oral & Maxillofacial Prosthodont, Jeddah 21589, Saudi Arabia
关键词
Aurorakinases; licensing proteins; prognosis; PREDICTIVE FACTORS; PROGNOSTIC VALUE; CYCLE KINETICS; CANCER; EXPRESSION; AURORA; MARKERS; PROTEIN; KINASE; METASTASIS;
D O I
10.1111/eos.12420
中图分类号
R78 [口腔科学];
学科分类号
1003 ;
摘要
Oral squamous cell carcinoma (OSCC) is still an unabated global killer with little advancement in its survival rate. DNA replication licensing proteins and Aurora kinase A are biomarkers that play important roles in genomic stability. The expression profile of minichromosomal maintenance protein 2 (MCM2), Ki67, geminin, and Aurora-A were linked to clinicopathological and outcome parameters, survival, and DNA content in 125 cases of OSCC. Oral fibroepithelial polyps (OFEP) were controls. The OSCC tumour cells were in a rapidly proliferating state, as assessed by the increased expression profile of MCM2, Ki67, geminin, and Aurora-A and of the geminin/Ki67 ratio, and the decrease of the MCM2/Ki67 ratio, in OSCC compared with OFEP (P < 0.000). There was an association between expression of MCM2, Ki67, and geminin and tumour histologic and invasive front grade (P < 0.05). A total of 82% of the OSCC assessed had aneuploid DNA content, which was associated with increased expression intensity of Aurora-A (P = 0.01). Geminin and the geminin/Ki67 ratio were associated with TNM staging (P < 0.05), and weak expression of MCM2, Ki67, geminin, and Aurora-A were predictive of OSCC survival (P < 0.05). Dysregulation of the origin licensing pathway and the mitotic pathway are important events in OSCC, and the combined analysis of these proteins may contribute to improved treatment decisions.
引用
收藏
页码:186 / 196
页数:11
相关论文
共 52 条
  • [1] Prognostic and predictive factors in oral cancer:: the role of the invasive tumour front
    Bànkfalvi, A
    Piffkò, J
    [J]. JOURNAL OF ORAL PATHOLOGY & MEDICINE, 2000, 29 (07) : 291 - 298
  • [2] DNA replication in eukaryotic cells
    Bell, SP
    Dutta, A
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 : 333 - 374
  • [3] Prognostic and predictive factors in oral squamous cell cancer:: important tools for planning individual therapy?
    Bettendorf, O
    Piffkò, J
    Bànkfalvi, A
    [J]. ORAL ONCOLOGY, 2004, 40 (02) : 110 - 119
  • [4] Preventing re-replication of chromosomal DNA
    Blow, JJ
    Dutta, A
    [J]. NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2005, 6 (06) : 476 - 486
  • [5] Replication licensing - defining the proliferative state?
    Blow, JJ
    Hodgson, B
    [J]. TRENDS IN CELL BIOLOGY, 2002, 12 (02) : 72 - 78
  • [6] PROGNOSTIC VALUE OF VARIOUS MOLECULAR AND CELLULAR-FEATURES IN ORAL SQUAMOUS-CELL CARCINOMAS - A REVIEW
    BRYNE, M
    [J]. JOURNAL OF ORAL PATHOLOGY & MEDICINE, 1991, 20 (09) : 413 - 420
  • [7] Expression of cyclin D1 and Ki-67 in squamous cell carcinoma of the oral cavity:: clinicopathological and prognostic significance
    de Vicente, JC
    Herrero-Zapatero, A
    Fresno, MF
    López-Arranz, JS
    [J]. ORAL ONCOLOGY, 2002, 38 (03): : 301 - 308
  • [8] Mcm2, Geminin, and Ki67 define proliferative state and are prognostic markers in renal cell carcinoma
    Dudderidge, TJ
    Stoeber, K
    Loddo, M
    Atkinson, G
    Fanshawe, T
    Griffiths, DF
    Williams, GH
    [J]. CLINICAL CANCER RESEARCH, 2005, 11 (07) : 2510 - 2517
  • [9] Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012
    Ferlay, J.
    Steliarova-Foucher, E.
    Lortet-Tieulent, J.
    Rosso, S.
    Coebergh, J. W. W.
    Comber, H.
    Forman, D.
    Bray, F.
    [J]. EUROPEAN JOURNAL OF CANCER, 2013, 49 (06) : 1374 - 1403
  • [10] Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012
    Ferlay, Jacques
    Soerjomataram, Isabelle
    Dikshit, Rajesh
    Eser, Sultan
    Mathers, Colin
    Rebelo, Marise
    Parkin, Donald Maxwell
    Forman, David
    Bray, Freddie
    [J]. INTERNATIONAL JOURNAL OF CANCER, 2015, 136 (05) : E359 - E386