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. 2015 Mar 25;10(3):e0121514.
doi: 10.1371/journal.pone.0121514. eCollection 2015.

Deregulated expression of Aurora kinases is not a prognostic biomarker in papillary thyroid cancer patients

Enke Baldini  1 , Chiara Tuccilli  1 , Natalie Prinzi  1 , Salvatore Sorrenti  2 , Laura Falvo  2 , Corrado De Vito  3 , Antonio Catania  2 , Francesco Tartaglia  2 , Renzo Mocini  2 , Carmela Coccaro  1 , Stefania Alessandrini  1 , Susi Barollo  4 , Caterina Mian  4 , Alessandro Antonelli  5 , Enrico De Antoni  2 , Massimino D'Armiento  1 , Salvatore Ulisse  1
Affiliations

Deregulated expression of Aurora kinases is not a prognostic biomarker in papillary thyroid cancer patients

Enke Baldini et al. PLoS One. .

Abstract

A number of reports indicated that Aurora-A or Aurora-B overexpression represented a negative prognostic factor in several human malignancies. In thyroid cancer tissues a deregulated expression of Aurora kinases has been also demonstrated, but no information regarding its possible prognostic role in differentiated thyroid cancer is available. Here, we evaluated Aurora-A and Aurora-B mRNA expression and its prognostic relevance in a series of 87 papillary thyroid cancers (PTC), with a median follow-up of 63 months. The analysis of Aurora-A and Aurora-B mRNA levels in PTC tissues, compared to normal matched tissues, revealed that their expression was either up- or down-regulated in the majority of cancer tissues. In particular, Aurora-A and Aurora-B mRNA levels were altered, respectively, in 55 (63.2%) and 79 (90.8%) out of the 87 PTC analyzed.A significant positive correlation between Aurora-A and Aurora-B mRNAs was observed (p=0.001). The expression of both Aurora genes was not affected by the BRAFV600E mutation. Univariate, multivariate and Kaplan-Mayer analyses documented the lack of association between Aurora-A or Aurora-B expression and clinicopathological parameters such as gender, age, tumor size, histology, TNM stage, lymph node metastasis and BRAF status as well as disease recurrences or disease-free interval. Only Aurora-B mRNA was significantly higher in T(3-4) tissues, with respect to T(1-2) PTC tissues. The data reported here demonstrate that the expression of Aurora kinases is deregulated in the majority of PTC tissues, likely contributing to PTC progression. However, differently from other human solid cancers, detection of Aurora-A or Aurora-B mRNAs is not a prognostic biomarker in PTC patients.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Expression of Aurora kinases in 87 papillary thyroid cancer tissues.
A and B) Variations in the expression of Aurora-A and Aurora-B in papillary thyroid cancer tissues. The fold changes were calculated considering the Aurora-A or Aurora-B mRNAs levels observed in normal matched thyroid tissue equal to 1. The statistical evaluation of the data was performed usingthe non-parametric Mann-Whitney test. The small bars in the graph indicate the median values. C) Correlation analysis of Aurora-A and Aurora-B mRNAs in PTC tissues. The data were evaluated by applying the Rho Spearman test.
Fig 2
Fig 2. Lack of effects of BRAFV600E on the expression of Aurora kinases.
A) Expression of Aurora-A and Aurora-B in papillary thyroid cancer tissues with wild type (n = 38) or mutated BRAF (n = 37). The fold changes were calculated considering the Aurora-A or Aurora-B mRNAs level observed in normal matched thyroid tissue equal to 1. The statistical evaluation of the data was performed by applying the non-parametric Mann Withney test. The small bars in the graph indicate the median values. B) Effect of BRAFV600E on Aurora kinases mRNAs in PCCL3 cells. The latter were induced to express BRAFV600E in a doxycycline-dependent manner. The fold changes of Aurora kinase mRNA were normalized against the non-treated cells.
Fig 3
Fig 3. Aurora kinase mRNA levels and disease-free interval (DFI) in papillary thyroid cancer patients.
Kaplan-Meier analysis combined with Mantel-Cox log-rank statistical test performed on 75 PTC patients followed-up from 8 to 133 months.
See this image and copyright information in PMC

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