Head-to-head comparison of the impact of Aurora A, Aurora B, Repp86, CDK1, CDK2 and Ki67 expression in two of the most relevant gynaecological tumor entities

Heilmann, Thorsten; Dittmann, Linda; Mackelenbergh, Marion van; Mundhenke, Christoph; Weimer, Jörg; Arnold, Norbert; Maass, Nicolaì; Schem, Christian

doi:10.1007/s00404-016-4104-z

Cited by 6 publications

(5 citation statements)

References 39 publications

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“…A German study performed in 93 ovarian benign and malignant tumour samples, showed hat the expression of AURKA, and AURKB among other cell cycle markers, were not predictive and were not associated with prognostic factors. 46 These results are in line with a second study 47 in 160 patients with primary EOC in which any AURKA immunostaining (score 1-3) was not predictive of impaired survival vs absence of expression (p=0.63).…”

Section: Aurk and Prognosis In Ocsupporting

confidence: 88%

Aurora kinases in ovarian cancer

et al. 2020

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Aurora kinases (AURK) are key regulators of the mitotic spindle formation. AURK is frequently overexpressed in ovarian cancer and this overexpression has been frequently associated with prognosis in these tumours. Interestingly, AURK have been shown to interact with DNA repair mechanisms and other cell cycle regulators. These functions have brought light to Aurora family as a potential target for anticancer therapy. In the last years, two clinical trials with different AURK inhibitors have shown activity in epithelial and clear-cell ovarian cancer. Although there is a lack of predictive factors of AURK inhibition activity, recent trials have identified some candidates. This review will focus in the functions of the AURK family, its role as prognostic factor in epithelial ovarian cancer and potential clinical implications.

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Section: Aurk and Prognosis In Ocsupporting

confidence: 88%

Aurora kinases in ovarian cancer

et al. 2020

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“…Cyclin-dependent kinase 1 (CDK1) plays an important role in the transition from G2 to M phase during the cell cycle [ 21 , 22 ], and multiple studies have verified that CDK1 acts as an oncogene. Indeed, CDK1 overexpression has been demonstrated in various tumors, including melanoma [ 23 ], pancreatic cancer [ 24 ], colon cancer [ 25 , 26 ], and mammary carcinoma [ 27 , 28 ]. In addition, some of these studies have shown that high CDK1 expression may be associated with poor prognosis in these malignancies.…”

Section: Discussionmentioning

confidence: 99%

Identification of potential core genes and pathways predicting pathogenesis in head and neck squamous cell carcinoma

Wang

Zhong

et al. 2021

Bioscience Reports

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Head and neck squamous cell carcinoma (HNSCC) is the most common subtype of head and neck cancer; however, its pathogenesis and potential therapeutic targets remain largely unknown. In this study, we analyzed three gene expression profiles and screened differentially expressed genes (DEGs) between HNSCC and normal tissues. The DEGs were subjected to gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), protein–protein interaction (PPI), and survival analyses, while the connectivity map (CMap) database was used to predict candidate small molecules that may reverse the biological state of HNSCC. Finally, we measured the expression of the most relevant core gene in vitro and examined the effect of the top predicted potential drug against the proliferation of HNSCC cell lines. Among the 208 DEGs and ten hub genes identified, CDK1 and CDC45 were associated with unfavorable HNSCC prognosis, and three potential small molecule drugs for treating HNSCC were identified. Increased CDK1 expression was confirmed in HNSCC cells, and menadione, the top predicted potential drug, exerted significant inhibitory effects against HNSCC cell proliferation and markedly reversed CDK1 expression. Together, the findings of this study suggest that the ten hub genes and pathways identified may be closely related to HNSCC pathogenesis. In particular, CDK1 and CDC45 overexpression could be reliable biomarkers for predicting unfavorable prognosis in patients with HNSCC, while the new candidate small molecules identified by CMap analysis provide new avenues for the development of potential drugs to treat HNSCC.

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“…The best would be, if those loci could use to predict the effectivity of drugs. Resistance to platinumbased chemotherapy is a significant clinical problem since patients with acquired resistance show a poor outcome in OvCa [14]. Developing a predictive tool to separate patients with platinum-resistant vs. platinum-sensitive tumours would be of potential advantage to disease management.…”

Section: Discussionmentioning

confidence: 99%

Evidence for predictive markers of platinum effectiveness in ovarian carcinoma by microarray-based comparative genomic hybridization

Weimer

Rohwer

Hedemann

et al. 2018

COGO

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Purpose: Seventy percent of all ovarian cancer (OvCa) diseases are diagnosed at an advanced stage due to poor screening methods. In general, the therapy consists of cyto-reductive surgery followed by first line platinum based chemo therapy, which frequently leads to a long-term response. A resistance against platinum therapy was detected in some cases by refractory recurrence within six months after the last donation. Identifying a marker predicting platinum effectiveness could be of great benefit for affected patients.Patients and methods: In this study we propose cyto-genetic procedures identifying markers of platinum resistance. Fresh tumor material was obtained from nine OvCa patients. After the last platinum-based chemotherapy, five patients had refractory recurrence within six month. DNA was isolated from tumor tissues for array-based comparative genomic hybridization (aCGH) analysis. Ten cultured metaphases per case were analyzed by spectral karyotyping (SKY) to detect repeated chromosome rearrangements. The obtained genomic data were correlated to the patients’ clinical follow-up data.Results: Eight chromosome aberrations correlated with recurrence later than six months were detected in tumors by SKY. Further seven chromosome aberrations correlated with a refractory recurrence. Non refractory tumors more frequently showed losses in 19q13.31-q13.42 by aCGH. Tumors with refractory recurrence more frequently showed gains in 17q21.32-17q24.3 and losses in 14q11.2, 9p22-p21.1, and 1p22.3-p22.1. OvCa showed separating cyto-genetic changes differentiated in platinum-refractory and non-refractory cases.Conclusion: Our results suggest that aCGH is the most suitable strategy for this, due to a significantly higher resolution. The loss in 19q13 correlated with better prognosis in OvCa

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Head-to-head comparison of the impact of Aurora A, Aurora B, Repp86, CDK1, CDK2 and Ki67 expression in two of the most relevant gynaecological tumor entities

Abstract: The prognostic value of the expression of Ki67 is overtrumped by alternative cell cycle kinases when it comes to prediction of axillary tumor spread and a shortened DFS, which might allow a further risk stratification in breast cancer patients.

Cited by 6 publications

References 39 publications

Aurora kinases in ovarian cancer

Aurora kinases in ovarian cancer

Identification of potential core genes and pathways predicting pathogenesis in head and neck squamous cell carcinoma

Evidence for predictive markers of platinum effectiveness in ovarian carcinoma by microarray-based comparative genomic hybridization

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