Dataset Information

Upregulation of centromere protein F is linked to aggressive prostate cancers.

ABSTRACT: Background:Centromere protein F (CENPF) is a key component of the kinetochore complex and plays a crucial role in chromosome segregation and cell cycle progression. Recent work suggests that CENPF upregulation is linked to aggressive tumor features in a variety of malignancies including prostate cancer. Materials and methods:Using a highly annotated tissue microarray, we analyzed CENPF protein expression from a cohort of 8,298 prostatectomized patients by immunohistochemistry to study its effect on prostate-specific antigen recurrence-free survival. Results:CENPF overexpression was found in 53% of cancers, and was linked to higher Gleason grade, advanced pathological tumor stage, accelerated cell proliferation, and lymph node metastasis (p<0.0001, each). A comparison with other key molecular features accessible through the microarray revealed strong associations between CENPF overexpression and presence of erythroblast transformation-specific (ETS)-related gene (ERG) fusion as well as phosphatase and tensin homolog deletion (p<0.0001, each). CENPF overexpression was linked to early biochemical recurrence. A subset analysis revealed that this was driven by the ERG-negative subset (p<0.0001). This was independent of established preoperative and postoperative prognostic parameters in multivariate analyses. Conclusion:The results of our study identify CENPF overexpression as an important mechanism and a potential biomarker for prostate cancer aggressiveness.

SUBMITTER: Gobel C

PROVIDER: S-EPMC6234994 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Upregulation of centromere protein F is linked to aggressive prostate cancers.

Göbel Cosima C Özden Cansu C Schroeder Cornelia C Hube-Magg Claudia C Kluth Martina M Möller-Koop Christina C Neubauer Emily E Hinsch Andrea A Jacobsen Frank F Simon Ronald R Sauter Guido G Michl Uwe U Pehrke Dirk D Huland Hartwig H Graefen Markus M Schlomm Thorsten T Luebke Andreas M AM

Cancer management and research 20181109

<h4>Background</h4>Centromere protein F (CENPF) is a key component of the kinetochore complex and plays a crucial role in chromosome segregation and cell cycle progression. Recent work suggests that CENPF upregulation is linked to aggressive tumor features in a variety of malignancies including prostate cancer.<h4>Materials and methods</h4>Using a highly annotated tissue microarray, we analyzed CENPF protein expression from a cohort of 8,298 prostatectomized patients by immunohistochemistry to s ...[more]

PMID: 30519097

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Project description:Background:A majority of prostate cancers (PCas) are indolent and cause no harm even without treatment. However, a significant proportion of patients with PCa have aggressive tumors that progress rapidly to metastatic disease and are often lethal. PCa develops through somatic mutagenesis, but emerging evidence suggests that germline genetic variation can markedly contribute to tumorigenesis. However, the causal association between genetic susceptibility and tumorigenesis has not been well characterized. The objective of this study was to map the germline and somatic mutation interaction landscape in indolent and aggressive tumors and to discover signatures of mutated genes associated with each type and distinguishing the two types of PCa. Materials and Methods:We integrated germline mutation information from genome-wide association studies (GWAS) with somatic mutation information from The Cancer Genome Atlas (TCGA) using gene expression data from TCGA on indolent and aggressive PCas as the intermediate phenotypes. Germline and somatic mutated genes associated with each type of PCa were functionally characterized using network and pathway analysis. Results:We discovered gene signatures containing germline and somatic mutations associated with each type and distinguishing the two types of PCa. We discovered multiple gene regulatory networks and signaling pathways enriched with germline and somatic mutations including axon guidance, RAR, WINT, MSP-RON, STAT3, PI3K, TR/RxR, and molecular mechanisms of cancer, NF-kB, prostate cancer, GP6, androgen, and VEGF signaling pathways for indolent PCa and MSP-RON, axon guidance, RAR, adipogenesis, and molecular mechanisms of cancer and NF-kB signaling pathways for aggressive PCa. Conclusion:The investigation revealed germline and somatic mutated genes associated with indolent and aggressive PCas and distinguishing the two types of PCa. The study revealed multiple gene regulatory networks and signaling pathways dysregulated by germline and somatic alterations. Integrative analysis combining germline and somatic mutations is a powerful approach to mapping germline and somatic mutation interaction landscape.

Dataset Information

Upregulation of centromere protein F is linked to aggressive prostate cancers.

Publications

Upregulation of centromere protein F is linked to aggressive prostate cancers.

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