Aurora‐A activation, correlated with hypoxia‐inducible factor‐1α, promotes radiochemoresistance and predicts poor outcome for nasopharyngeal carcinoma

Abstract

Previously, we and others showed that hypoxia-inducible factor-1a (HIF-1a) and transcriptionally upregulated Aurora-A were required for disease progression in several tumors. Here, we address the clinicopathologic value of Aurora-A and HIF-1a in locally advanced nasopharyngeal carcinoma (NPC). Aurora-A and HIF-1a expression was semiquantitatively evaluated by immunohistochemistry staining in 144 cases from a randomized controlled trial. Of these patients, 69 received neoadjuvant chemotherapy plus concurrent chemoradiotherapy, and acted as the training set, and 75 cases treated with neoadjuvant chemotherapy plus radiotherapy were used as the testing set to validate the prognostic effect of Aurora-A and HIF-1a. We found that Aurora-A and HIF-1a were highly expressed in NPC, but were deficient in normal adjacent epithelia. In the testing set, Aurora-A overexpression predicted a shortened 5-year overall survival (59.1% vs 82.5%, P = 0.024), progressionfree survival (44.8% vs 79.8%, P = 0.004), and distant metastasisfree survival (43.0% vs 17.3%, P = 0.016). Multivariate regression analysis confirmed that Aurora-A was indeed an independent prognostic factor for death, recurrence, and distant metastasis both in the testing set and overall patients. Moreover, a positive correlation between Aurora-A and HIF-1a was detected (P = 0.037). Importantly, although HIF-1a did not show any prognostic effect for patient outcome, the subset with Aurora-A and HIF-1a co-overexpression had the poorest overall, progression-free, and distant metastasis-free survival (all P < 0.05). Our results confirmed that Aurora-A was an independent prognostic factor for NPC. Aurora-A combined with HIF-1a refined the risk definition of the patient subset, thus potentially directing locally advanced NPC patients for more selective therapy. (Cancer Sci 2012; 103: 1586-1594

Genetic Variations in the HIF1A Gene Modulate Response to Adjuvant Chemotherapy after Surgery in Patients with Colorectal Cancer

“…Previous studies have found that HIF-1α overexpression indicates unfavorable prognosis and may serve as an potential prognostic factor in several cancers (Zhong et al, 1999;Marton et al, 2012;Wan et al, 2012;Li et al, 2013;Luan et al, 2013;Zhang et al, 2013;), including colon, breast , gastric, lung , skin, ovarian, pancreatic, prostate, and renal carcinomas. Furthermore, down-regulated HIF-1α expression in transplanted esophageal squamous cell carcinoma in vivo could enhance the cytotoxicity of cisplatin (Liao et al, 2012).…”

Prognostic value of Aurora kinase A (AURKA) expression among solid tumor patients: a systematic review and meta-analysis

“…All eligible studies were published between 2005 and 2014. All TNM Stages (I-IV) were considered in 18 studies (46.2%) (9,18,20,27,28,30,(34)(35)(36)(37)(38)40,43,44,50,55,56,58), non-metastatic solid tumors (including Stage I-III or localized disease, based solely on singlestage disease or mixture of tumor stages) were considered in 12 (30.8%) studies (22,29,31,33,39,41,42,46,48,51,53,54); metastatic solid tumors (Stage IV) patients were considered in four studies (10.2%) (23,45,49,57); disease stage was not available were considered in five studies (12.8%). Four studies analyzing AURKA mRNA expression used real-time reverse transcription PCR (RT-PCR) (20,34,35,45); one study analyzing AURKA gene amplification by fluorescence in situ hybridization (FISH) (54); the other one used immunohistochemical (IHC) staining and RT-PCR (47); and the remaining 33 studies applied a immunohistochemistry detection method (9,18,19,21-23,27-33, 36-44,46,48-53,55-58).…”

“…Four studies analyzing AURKA mRNA expression used real-time reverse transcription PCR (RT-PCR) (20,34,35,45); one study analyzing AURKA gene amplification by fluorescence in situ hybridization (FISH) (54); the other one used immunohistochemical (IHC) staining and RT-PCR (47); and the remaining 33 studies applied a immunohistochemistry detection method (9,18,19,21-23,27-33, 36-44,46,48-53,55-58). Eight studies were conducted in patients from European countries (19,21,28,32,36,40,55,57), four in patients from USA (18,20,37,45), three in Oceania countries (33,46,49), one in South America (50), and twenty-three in Asian countries (9,22,23,27,(29)(30)(31)34,35,38,39,(41)(42)(43)(44)47,48,(51)(52)(53)(54)56,58). One or more oncologic outcome parameters were analyzed on multivariate analysis in 33 studies <...>…”

Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging

“…There are more published studies that evaluated pathological hypoxic markers in NPC ( Table 1) (36)(37)(38)(39)(40)(41)(42)(43). Most studies evaluated HIF-1α expression which was found in 32-83% of patients ( Table 1).…”