P4. Aurora kinase MRNA level and gene copy number alterations in stage I-III. A non-small cell lung cancer

Background: Mitotic regulators Aurora kinases are up-regulated in different malignancies and seem to be involved in tumorigenesis. Their status in non-small cell lung cancer (NSCLC) remains poorly investigated. We aimed to examine mRNA level and copy number (CN) alterations of Aurora kinase-encoding genes in surgical NSCLC specimens in terms to patients’ clinicopathological characteristics and survival.

Materials and methods: A total of 148 patients were included into the analysis. mRNA and gene CN were evaluated in paired tumor and unaffected lung specimens with a comparative quantitative real-time PCR method.

Results: A significant increase in AURKA and AURKB mRNA level in tumor compared to a matched unaffected lung was observed (about four-fold for AURKA and eight-fold for AURKB; P<0.001 for both). High expression correlated with a high histological grade (P=0.033 and P<0.001 for AURKA and AURKB, respectively) and trended to be associated with a more advanced pathological stage (P>0.05). No AURKC expression in cancer and normal tissues was found. About 45% of tumors revealed an increase in AURKA CN above the diploid number with a median of 2.37 copies per cell (range, 0.88-6.32). AURKB CN gain was observed in 16.0% of NSCLCs, with a significantly higher incidence in stage IIIA tumors as compared to stage (I+II) tumors (P<0.001). There was no correlation between gene CN and mRNA level for both the kinases. High AURKB mRNA level was associated with poor survival in a univariate analysis with a log-rank test, however, only in patients with moderately- or highly-differentiated tumors (P=0.003) and was also an independent negative prognostic factor in a multivariate analysis in a Cox proportional hazards model (P=0.009). In the whole patients’ cohort a trend towards poor survival was observed (P=0.066).

Conclusions: AURKA and AURKB are highly up-regulated in NSCLCs, especially in poorly-differentiated tumors. Although gene CN gains occur frequently, other molecular mechanisms are responsible for gene activation. In NSCLC patients with differentiated tumors, AURKB mRNA level is prognostic for survival.

Keywords: Non-small cell lung cancer (NSCLC); Aurora kinase; classification