Chromosomal Instability in Cell-Free DNA Is a Serum Biomarker for Prostate Cancer

Schütz, Ekkehard; Akbari, Mohammad Reza; Beck, Julia; Urnovitz, Howard B.; Zhang, William W.; Bornemann-Kolatzki, Kirsten; Mitchell, William M.; Nam, Robert K.; Narod, Steven A.

doi:10.1373/clinchem.2014.226571

Cited by 42 publications

(28 citation statements)

References 38 publications

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“…Recent studies have explored the utility of copy number variations presenting in cell-free DNA (cfDNA) fragments in serum/ plasma as a potential clinically useful biomarker to detect prostate cancer, giving a diagnostic accuracy of 83% [13]. With the whole-genome analyses of cfDNA, Leary, et al identified chromosomal alterations present in all plasma of advanced-stage cancer patients [12].…”

Section: Introductionmentioning

confidence: 99%

A Novel Method to Detect Early Colorectal Cancer Based on Chromosome Copy Number Variation in Plasma

Kang

Ma³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Colonoscopy screening has been accepted broadly to evaluate the risk and incidence of colorectal cancer (CRC) during health examination in outpatients. However, the intrusiveness, complexity and discomfort of colonoscopy may limit its application and the compliance of patients. Thus, more reliable and convenient diagnostic methods are necessary for CRC screening. Genome instability, especially copy-number variation (CNV), is a hallmark of cancer and has been proved to have potential in clinical application. Methods: We determined the diagnostic potential of chromosomal CNV at the arm level by whole-genome sequencing of CRC plasma samples (n = 32) and healthy controls (n = 38). Arm level CNV was determined and the consistence of arm-level CNV between plasma and tissue was further analyzed. Two methods including regular z score and trained Support Vector Machine (SVM) classifier were applied for detection of colorectal cancer. Results: In plasma samples of CRC patients, the most frequent deletions were detected on chromosomes 6, 8p, 14q and 1p, and the most frequent amplifications occurred on chromosome 19, 5, 2, 9p and 20p. These arm-level alterations detected in plasma were also observed in tumor tissues. We showed that the specificity of regular z score analysis for the detection of colorectal cancer was 86.8% (33/38), whereas its sensitivity was only 56.3% (18/32). Applying a trained SVM classifier (n = 40 in trained group) as the standard to detect colorectal cancer relevance ratio in the test samples (n = 30), a sensitivity of 91.7% (11/12) and a specificity 88.9% (16/18) were finally reached. Furthermore, all five early CRC patients in stages I and II were successfully detected. Conclusion: Trained SVM classifier based on arm-level CNVs can be used as a promising method to screen early-stage CRC.

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Section: Introductionmentioning

confidence: 99%

A Novel Method to Detect Early Colorectal Cancer Based on Chromosome Copy Number Variation in Plasma

Kang

Ma³

et al. 2018

Cell Physiol Biochem

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“…Therefore, additional predictive factors of prognosis are needed to better evaluate therapy outcomes and help develop individualized treatment plans. Several methods have been used to identify new biomarkers for CRC, including translational approaches investigating perturbations in gene expression or genomic instability, which can be identified using animal models of CRC [21], and high-throughput technologies such as massive parallel sequencing [22]. Bioinformatics methods combined with public cancer databases also have been widely used to find potential biomarkers.…”

Section: Discussionmentioning

confidence: 99%

TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis

Liu

Wang

et al. 2016

Oncotarget

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Colorectal carcinoma (CRC) is a malignant epithelial tumour with tremendous invasion and metastatic capacity. Transforming acidic coiled-coil protein-3 (TACC3), a frequently aberrantly expressed oncogene, is an important biomarker in various human cancers. Our study aimed to investigate the expression and function of TACC3 in human CRC. We found that TACC3 was over-expressed at both the mRNA and protein levels in CRC cells and in biopsies of CRC tissues compared with normal controls as determined by qRT-PCR, western blot and immunohistochemical (IHC) staining assays. IHC staining of samples from 161 patients with CRC also revealed that TACC3 expression was significantly correlated with clinical stage (P = 0.045), T classification (P = 0.029) and M classification (P = 0.020). Multivariate analysis indicated that high TACC3 expression was an independent prognostic marker for CRC. Patients who had high TACC3 expression had significantly poorer overall survival (OS, P = 0.023) and disease-free survival (DFS, P = 0.019) compared to patients who had low TACC3 expression. Furthermore, TACC3 knockdown attenuated CRC cell proliferation, colony formation capability, migration and invasion capability, and tumourigenesis in nude mice; these properties were measured using a real-time cell analyser (RTCA), clonogenicity analysis, and transwell and xenograft assays, respectively. These data indicate that TACC3 promotes CRC progression and could be an independent prognostic factor and a potential therapeutic target for CRC.

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“…In this view, the analysis of the genomic instability resulting in copy number aberrations through massive parallel sequencing, as already demonstrated for prostate cancer [11] or the detection of tumorderived circulating cell-free DNA in plasma samples [12] could represent new possibilities for the detection and monitoring of CRC to investigate in the AOM/DSS murine model.…”

Section: Introductionmentioning

confidence: 99%

Novel insights into Notum and glypicans regulation in colorectal cancer

Robertis¹,

Arigoni²,

Loiacono³

et al. 2016

European Journal of Cancer

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The connection between colorectal cancer (CRC) and Wnt signaling pathway activation is well known, but full elucidation of the underlying regulation of the Wnt/β-catenin pathway and its biological functions in CRC pathogenesis is still needed. Here, the azoxymethane/dextran sulfate sodium salt (AOM/DSS) murine model has been used as an experimental platform able to mimic human sporadic CRC development with predictable timing. We performed genome-wide expression profiling of AOM/DSS-induced tumors and normal colon mucosa to identify potential novel CRC biomarkers. Remarkably, the enhanced expression of Notum, a conserved feedback antagonist of Wnt, was observed in tumors along with alterations in Glypican-1 and Glypican-3 levels. These findings were confirmed in a set of human CRC samples. Here, we provide the first demonstration of significant changes in Notum and glypicans gene expression during CRC development and present evidence to suggest them as potential new biomarkers of CRC pathogenesis.

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Chromosomal Instability in Cell-Free DNA Is a Serum Biomarker for Prostate Cancer

Cited by 42 publications

References 38 publications

A Novel Method to Detect Early Colorectal Cancer Based on Chromosome Copy Number Variation in Plasma

A Novel Method to Detect Early Colorectal Cancer Based on Chromosome Copy Number Variation in Plasma

TACC3 promotes colorectal cancer tumourigenesis and correlates with poor prognosis

Novel insights into Notum and glypicans regulation in colorectal cancer

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