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Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma.

ABSTRACT: BACKGROUND:Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea. METHODS:AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues. RESULTS:AURKA gene amplification was found more frequently in the 20q13.2-13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001). CONCLUSIONS:AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients.

SUBMITTER: Koh HM

PROVIDER: S-EPMC5267544 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma.

Koh Hyun Min HM Jang Bo Geun BG Hyun Chang Lim CL Kim Young Sill YS Hyun Jin Won JW Chang Weon Young WY Maeng Young Hee YH

Journal of pathology and translational medicine 20161225 1

<h4>Background</h4>Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea.<h4>Methods</h4>AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological char ...[more]

PMID: 28013532

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Project description:BackgroundMalignant mesothelioma (MM) is a highly aggressive cancer with a poor prognosis. Despite the use of several well-known markers, the diagnosis of MM is still challenging in some cases. we applied bioinformatics to identify key genes and screen for diagnostic and prognostic markers of MM.MethodsThe expression profiles of GSE2549 and GSE112154 microarray datasets from the Gene Expression Omnibus database contained 87 cases of MM tissue and 8 cases of normal mesothelial tissue in total. The GEO2R tool was used to detect differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed using DAVID Bioinformatics Resources. The DEGs protein-protein interaction networks were constructed from the STRING database. Cytoscape was used to identify significant modules and hub genes. The GEPIA database was used to explore relationships between hub genes and prognosis of MM. Immunohistochemistry was used to analyze protein expression in tissue microarrays with 47 Chinese MM tissues. Statistical analyses diagnostic and prognostic values.Results346 DEGs were identified: 111 genes upregulated, and 235 downregulated. GO analysis showed that the primary biological processes of these DEGs were cell adhesion, leukocyte migration, and angiogenesis. The main cellular components included the extracellular space, extracellular exosome, and extracellular region. The molecular functions were integrin binding, heparin binding, and calcium ion binding. KEGG pathway analysis showed that DEGs are primarily involved in PPAR signaling pathway, extracellular matrix-receptor interactions, and regulation of lipolysis in adipocytes. Survival analysis showed that seven genes-AURKA, GAPDH, TOP2A, PPARG, SCD, FABP4, and CEBPA-may be potential prognostic markers for MM. Immunohistochemical studies showed that Aurora kinase A (AURKA gene encode, Aurora-A) and GAPDH were highly expressed in MM tissue in comparison with normal mesothelial tissue. Kaplan-Meier analysis confirmed a correlation between Aurora-A protein expression and overall survival but did not confirm a correlation with GAPDH. The receiver operating characteristic curves of Aurora-A protein expression suggested acceptable accuracy (AUC = 0.827; 95% CI [0.6686 to 0.9535]; p = 0.04). The sensitivity and specificity of Aurora-A were 83.33% and 77.78%, respectively.ConclusionAurora-A could be an optimal diagnostic biomarker and a potential prognostic marker for MM.

Project description:Background Lung adenocarcinoma (LUAD) accounts for the largest proportion of lung cancer patients and has the highest morbidity and mortality worldwide. Accumulating evidence shows that immune-associated long non-coding RNAs (lncRNAs) play a role in LUAD, although their predictive value for immunotherapy treatment and cancer-related death remains poorly investigated. Methods Gene expression profiles and clinical data were obtained from The Cancer Genome Atlas. We constructed a risk model by univariate and multivariate Cox regression and least absolute shrinkage and selection operator regression analysis and subsequently divided each sample into low- or high-risk category. Survival and receiver operating characteristic (ROC) analyses were applied to assess the prognostic value of the model. Additionally, immune and somatic mutation status were analysed between the two risk groups. Finally, the model was applied to pancreatic ductal adenocarcinoma (PDAC) samples to explore the applicability of the model in other cancers. Results We obtained data from 499 LUAD patients and randomised the samples into a training set (N=351) and validation set (N=148) at a 7:3 ratio. We detected 7 immune-associated lncRNAs (AP000695.2, AC026355.2, LINC01843, ITGB1-DT, LINC01150, AL590226.1 and AC091185.1) that were applicable for establishing a risk signature. Survival analysis revealed that patients categorised in the high-risk group had shorter overall survival (OS) than those in the low-risk group. ROC analyses showed excellent AUC values in all data sets (>0.65 at 1, 3, and 5 years). Notably, ESTIMATE algorithm and analysis of PCA, (ss)GSEA, and somatic mutations revealed that the high-risk group had a stronger immunosuppressive status and a higher tumour mutation burden (TMB). Moreover, patients in the low-risk group responded better to immunotherapy due to higher levels of immune-checkpoint receptor genes and TLS-related genes. Our model using the 7 immune-associated lncRNAs showed similar applicability for PDAC patients. Conclusions We constructed a model for risk signatures based on 7 immune-associated lncRNAs and showed its prognostic value for identifying immune and somatic mutation characteristics in LUAD patients, which may assist clinical treatment plans and elucidate molecular mechanisms of LUAD immunity.

Dataset Information

Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma.

Publications

Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma.

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