Prognosis value of mitotic kinase Aurora-A for primary duodenal adenocarcinoma

• Published in: Tumor biology 2014-09, Vol.35 (9), p.9361-9370
• Main Authors: Chen, Jie, Lin, Qu, Wen, Jing-Yun, Li, Xing, Ma, Xiao-Kun, Fan, Xin-Juan, Cao, Qin-Hua, Dong, Min, Wei, Li, Chen, Zhan-Hong, Li, Xiao-Yun, Wang, Tian-Tian, Liu, Quentin, Wan, Xiang-Bo, Xing, Yan-Fang, Wu, Xiang-Yuan
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - enzymology; Aurora Kinase A - metabolism; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Blotting, Western; Cancer Research; Chemotherapy; Duodenal Neoplasms - diagnosis; Duodenal Neoplasms - enzymology; Female; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Immunohistochemistry; Immunohistochemistry - statistics & numerical data; Kaplan-Meier Estimate; Kidney cancer; Kinases; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Research Article; ROC Curve
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-014-2215-3

Others and we have demonstrated that hypoxia-inducible factor 1α (HIF-1α) and transcriptionally upregulated Aurora-A are required for disease progression in several tumors. We investigated the clinicopathological value of HIF-1α and Aurora-A in primary duodenal adenocarcinoma (PDA). Using immunohistochemistry, we evaluated Aurora-A and HIF-1α expression semiquantitatively in 140 PDA cases. There were 76 cases from one institute that formed the training set; 64 cases from another two institutes were used as the testing set to validate the prognostic value of Aurora-A and HIF-1α expression. Aurora-A expression was high or sufficient in the tumor zone, whereas expression was low in the adjacent normal epithelia. High Aurora-A expression, identified using the training set receiver operator characteristic (ROC) analysis-generated cutoff score, predicted poorer overall survival both in the testing set (18.0 vs. 45.1 %, P  = 0.001) and training set (23.1 vs. 53.9 %, P  = 0.011). Multivariate Cox regression confirmed that Aurora-A was an independent prognostic factor. Contrary to previous studies, we did not detect any correlation between Aurora-A and HIF-1α. Survival analysis showed that HIF-1α level was not correlated with patient outcome ( P  = 0.466). Activation of Aurora-A, an independent negative prognostic biomarker, might be used to identify particular PDA patients for more selective therapy.