The Aurora Kinase A Polymorphisms are not Associated with Recurrence-free Survival in Prostate Cancer Patients

Abstract

Background: The purpose of this study was to investigate the association between haplotype-tagging single nucleotide polymorphisms (SNPs) within the Aurora Kinase A (AURKA) gene and prostate cancer outcomes in patients with clinically localized prostate cancer. Methods:Four intronic haplotype-tagging SNPs within the AURKA gene were individually selected and examined in regard to their influence on clinical outcomes in 212 patients who underwent radical prostatectomy as first-line treatment. Haplotype-tagging SNPs were selected using the ABI SNP Browser to cover SNPs with an r 2 of 0.90 or greater in the AURKA gene with a minor allele frequency of at least 0.25. Results:In our study, a log-rank univariate analysis was performed to identify significant associations between probability of recurrence-free survival or disease-free survival and known prognostic indicators as well as AURKA genotypes. The prognostic indicators Gleason grade, surgical margin, extracapsular extension, and disease stage were associated with recurrence-free survival (all p<0.001). Only Gleason grade was associated with disease-free survival (p<0.001). No associations were found for the SNPs rs1468055, rs8117896, rs2064863, and rs1468056 analyzed for either RFS (p=0.7213, p=0.5140, p=0.0714, p=0.4731, respectively) or DFS (p=0.3282, p=0.1909, p=0.4111, p=0.5014, respectively). Clinical data on patient follow-up at Vanderbilt University Medical Center were retrospectively gathered via electronic medical records. The mean follow-up for disease-free survival and assessment of prostate cancer progression were 8.3 ± 2.4-y and 4.4 ± 3.9-y, respectively. The endpoints analyzed were recurrence-free survival (RFS) and diseasefree survival (DFS). Recurrence post-prostatectomy was classified as biochemical (which has been shown to be a poor predictor of overall survival in patients with localized prostate cancer treated with radical prostatectomy) [14], local or distant, and the most advanced recurrence type documented was assigned to each patient. Biochemical recurrence was defined as a prostate-specific antigen (PSA) detection of > 0.1 ng/ ml in at least two consecutive tests. DFS was defined as the length of time between the date of prostatectomy to the date of death or last follow-up. Conclusions Genotyping of Aurora Kinase A polymorphisms in prostate cancer samplesProstatectomy specimens were processed and genomic DNA extracted from deparaffinizedspecimens as described previously [15]. Purified genomic DNA was genotyped for the following haplotypetagging SNPs in the AURKA gene: rs1468055, rs8117896, rs2064863, and rs1468056. Haplotype-tagging SNPs (htSNPs) were selected using the ABI SNP Browser to cover SNPs with an r 2 of 0.90 or greater in the AURKA gene with a minor allele frequency (MAF) of at least 0.25. A total of 4 SNPs were selected and genotyped in our patient cohort. Allelic discrimination of these AURKA polymorphisms was performed using Taqman SNP genotyping assays (Applied Biosystems: and C_8947664_10 [rs1468056]). The fina...

Single nucleotide polymorphisms rs911160 in AURKA and rs2289590 in AURKB mitotic checkpoint genes contribute to gastric cancer susceptibility

“…For example, rs2273535 (Phe31Ile) has been associated with colorectal, breast, lung, and esophageal cancer risk [Kimura et al, 2005;Lo et al, 2005;Cox et al, 2006;Hienonen et al, 2006;Chen et al, 2007;Gu et al, 2007;Vidarsdottir et al, 2007]. Similarly, rs1047972 (Ile57Val) significantly increased the risk of esophageal cancer development, as well as the risk of gastric cancer and its progression [Kimura et al, 2005;Ju et al, 2006;Jaboin et al, 2012;Mesic et al, 2016]. In addition, it was demonstrated that rs1047972 could enhance AURKA relative kinase activity [Ju et al, 2006].…”

“…Aurora kinase A ( AURKA ) is a serine/threonine kinase and well known oncogene, which plays an important role in centrosome maturation and separation, chromosome alignment, mitotic spindle assembly, mitotic entry and cytokinesis [Fu et al, ; Tchatchou et al, ; Jaboin et al, ; Gavriilidis et al, ]. Aurora kinase B ( AURKB ) is part of the chromosomal passenger complex (CPC), which regulates histone modification, chromatid segregation and cytokinesis [Bolton et al, ; Honda et al, ; Vader et al, ].…”

“…Genetic variations, mutations and aberrant expression of mitotic checkpoint genes could induce CIN and aneuploidy, leading to the development of cancer [Frank, 2004;Duesberg et al, 2005;Hudler, 2012]. alignment, mitotic spindle assembly, mitotic entry and cytokinesis [Fu et al, 2007;Tchatchou et al, 2007;Jaboin et al, 2012;Gavriilidis et al, 2015]. Aurora kinase B (AURKB) is part of the chromosomal passenger complex (CPC), which regulates histone modification, chromatid segregation and cytokinesis [Bolton et al, 2002;Honda et al, 2003;Vader et al, 2006].…”

Association of theAURKAandAURKCgene polymorphisms with an increased risk of gastric cancer

“…One of the most studied functional AURKA SNP is rs2273535, which was found to be associated with the disease risk in multiple tumor types including colon, breast, lung, and esophagus (57)(58)(59)(60)(61)(62)(63). Another functional AURKA SNP is rs1047972, which was associated with the risk of esophagus cancer as well as with GC progression among the diffuse type patients (16,41). It has been suggested that rs1047972 enhances relative kinase activity of AURKA.…”

“…Mammalian cells have three types of Aurora kinases, AURKA, AURKB, and AURKC which have specific subcellular localizations and functions during cell cycle . Aurora kinase A (AURKA) is a well‐known oncogene and serin/threonin kinase , which is localized at the centrosome from the moment of centrosome duplication to mitotic completion, and separates to the spindle poles and spindle microtubules during mitotic division . Therefore, AURKA plays pivotal role in centrosome function and spindle assembly .…”