Expression and prognostic value of the cell polarity PAR complex members in thyroid cancer

Tuccilli,Chiara; Baldini,Enke; Arlot-Bonnemains,Yannick; Chesnel,Frank; Sorrenti,Salvatore; De Vito,Corrado; D'Armiento,Eleonora; Antonelli,Alessandro; Fallahi,Poupak; Watutantrige,Sara; Tartaglia,Francesco; Barollo,Susi; Mian,Caterina; Arcieri,Stefano; Mascagni,Domenico; Pironi,Daniele; Bononi,Marco; Vergine,Massimo; Monti,Massimo; Filippini,Angelo; Ulisse,Salvatore

doi:10.3892/ijo.2017.3907

Expression and prognostic value of the cell polarity PAR complex members in thyroid cancer

Authors:
- Chiara Tuccilli
- Enke Baldini
- Yannick Arlot-Bonnemains
- Frank Chesnel
- Salvatore Sorrenti
- Corrado De Vito
- Eleonora D'Armiento
- Alessandro Antonelli
- Poupak Fallahi
- Sara Watutantrige
- Francesco Tartaglia
- Susi Barollo
- Caterina Mian
- Stefano Arcieri
- Domenico Mascagni
- Daniele Pironi
- Marco Bononi
- Massimo Vergine
- Massimo Monti
- Angelo Filippini
- Salvatore Ulisse
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Affiliations: Department of Experimental Medicine, ʻSapienzaʼ University of Rome, Rome, Italy, Department of Surgical Sciences, ʻSapienzaʼ University of Rome, Rome, Italy, CNRS-UMR 6290 (IGDR) Université Rennes 1, Rennes, France, Department of Public Health and Infectious Diseases, ʻSapienzaʼ University of Rome, Rome, Italy, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, Department of Medicine, University of Padua, Padua, Italy, Department of Surgery ʻPietro Valdoniʼ, ʻSapienzaʼ University of Rome, Rome, Italy
Published online on: March 8, 2017 https://doi.org/10.3892/ijo.2017.3907
Pages: 1413-1422

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Abstract

Establishment and maintenance of the apical-basal cell polarity, required for proper replication, migration, specialized functions and tissue morphogenesis, relies on three evolutionary conserved complexes: PAR, CRUMBS and SCRIBBLE. Loss of cell polarity/cohesiveness (LOP/C) is implicated in cancer progression, and members of the polarity complex have been described as either oncogenes or oncosuppressors. However, no information on their role in thyroid cancer (TC) progression is available. In the present study, we evaluated the gene expression of the PAR complex members aPKCι, PARD3α/β and PARD6α/β/γ in 95 papillary TC (PTC), compared to their normal matched tissues and in 12 anaplastic TC (ATC). The mRNA and protein levels of investigated genes were altered in the majority of PTC and ATC tissues. In PTC, univariate analysis showed that reduced expression of aPKCι, PARD3β and PARD6γ mRNAs is associated with increased tumor size, and the reduced expression of PARD3β mRNA is associated also with recurrences. Multivariate analysis demonstrated that the presence of lymph node metastasis at diagnosis and the reduced expression of PARD3β are independent risk factors for recurrences, with hazard ratio, respectively, of 8.21 (p=0.006) and 3.04 (p=0.029). The latter result was confirmed by the Kaplan-Meier analysis, which evidenced the association between decreased PARD3β mRNA levels and shorter disease-free interval. In conclusion, we demonstrated that the expression of PAR complex components is deregulated in the majority of PTC and there is a general trend towards their reduction in ATC tissues. Moreover, a prognostic value for the PARD3β gene in PTCs is suggested.

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