The performance of the SEPT9 gene methylation assay and a comparison with other CRC screening tests: A meta-analysis

Song, Lele; Jia, Jia; Peng, Xiumei; Wu, Xiao; Li, Yuemin

doi:10.1038/s41598-017-03321-8

Cited by 125 publications

(126 citation statements)

References 32 publications

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“…An improved understanding of the mechanisms and processes underlying resistance formation is necessary to identify biomarkers that guide the use of efficient next-line therapies for tumours that have do not respond to the available standard therapies anymore of liquid biopsies still faces many technological and methodological challenges [24,25] . However, the first FDA-approved assays based on liquid biopsies are available and have been shown to improve therapy outcomes [24,[26][27][28][29][30][31][32] .…”

Section: Preclinical Model Systems Are Needed To Deliver Biomarkers Fmentioning

confidence: 99%

Drug-adapted cancer cell lines as preclinical models of acquired resistance

Michaelis¹,

Wass²,

Činátl³

2019

CDR

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Acquired resistance formation limits the efficacy of anti-cancer therapies. Acquired and intrinsic resistance differ conceptually. Acquired resistance is the consequence of directed evolution, whereas intrinsic resistance depends on the (stochastic) presence of pre-existing resistance mechanisms. Preclinical model systems are needed to study acquired drug resistance because they enable: (1) in depth functional studies; (2) the investigation of non-standard treatments for a certain disease condition (which is necessary to identify small groups of responders); and (3) the comparison of multiple therapies in the same system. Hence, they complement data derived from clinical trials and clinical specimens, including liquid biopsies. Many groups have successfully used drug-adapted cancer cell lines to identify and elucidate clinically relevant resistance mechanisms to targeted and cytotoxic anti-cancer drugs. Hence, we argue that drug-adapted cancer cell lines represent a preclinical model system in their own right that is complementary to other preclinical model systems and clinical data.

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Section: Preclinical Model Systems Are Needed To Deliver Biomarkers Fmentioning

confidence: 99%

Drug-adapted cancer cell lines as preclinical models of acquired resistance

Michaelis¹,

Wass²,

Činátl³

2019

CDR

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“…A prospective trial evaluating screening in asymptomatic individuals showed a CRC detection rate up to 48.2% and specificity of 91.5% (24). A large meta-analysis has also confirmed the utility of SEPT9 promoter methylation measurement in the detection of cancer amongst symptomatic patients, with the test showing superiority to that of protein and fecal immunohistochemical testing (20). In asymptomatic patients, the sensitivity and specificity of the test was lower than FIT, underscoring the need for further research and refinement of methods as well as the careful selection of the algorithm in which to define the threshold for SEPT9 methylation detection (20).…”

Section: Diagnostic Applications Of Dna Methylation Assaysmentioning

confidence: 90%

“…A large meta-analysis has also confirmed the utility of SEPT9 promoter methylation measurement in the detection of cancer amongst symptomatic patients, with the test showing superiority to that of protein and fecal immunohistochemical testing (20). In asymptomatic patients, the sensitivity and specificity of the test was lower than FIT, underscoring the need for further research and refinement of methods as well as the careful selection of the algorithm in which to define the threshold for SEPT9 methylation detection (20). Despite data supporting its use as a diagnostic tool, from a large-scale screening perspective SEPT9 methylation status is still considered inferior to other modalities, and is only recommended for patients who refuse other options (25).…”

Section: Diagnostic Applications Of Dna Methylation Assaysmentioning

confidence: 90%

“…Hypermethylation of CpG island 3 in the promoter of the SEPT9 gene can be detected through its release into the peripheral blood from necrotic and apoptotic cancer cells. Thus, detection of SEPT9 methylation reflects the likely presence of CRC (20,21). Initial studies evaluating the detection of SEPT9 promoter methylation in the plasma of CRC patients reported a sensitivity of 72% and specificity of 90% (22,23).…”

Section: Diagnostic Applications Of Dna Methylation Assaysmentioning

confidence: 99%

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Epigenetics and Precision Oncology

2017

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Epigenetic alterations such as DNA methylation defects and aberrant covalent histone modifications occur within all cancers and are selected for throughout the natural history of tumor formation with changes being detectable in early onset, progression and, ultimately, recurrence and metastasis. The ascertainment and use of these marks to identify at-risk patient populations, refine diagnostic criteria, and provide prognostic and predictive factors to guide treatment decisions is of growing clinical relevance. Further, the targetable nature of epigenetic modifications provides a unique opportunity to alter treatment paradigms and provide new therapeutic options for patients whose malignancies possess these aberrant epigenetic modifications, paving the way for new and personalized medicine. DNA methylation has proven to be of significant clinical utility for its stability and relative ease of testing. The intent of this review is to elaborate upon well-supported examples of epigenetic precision medicine and how the field is moving forward, primarily in the context of aberrant DNA methylation.

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“…Epigenetic silencing of the SEPT9 gene by promoter methylation in cell-free plasma has been shown to be a biomarker for CRC [12,16,17]. Using high-sensitivity Real-Time PCR methods, hypermethylated SEPT9 DNA signatures can be detected in cellfree plasma [12,[19][20][21][22][23][24][25][26][27]. As an early event and hallmark of human cancers, aberrant DNA methylation biomarkers have clinical roles in screening, diagnosis, prognosis and therapeutic response [11,28].…”

Section: Clinicalmentioning

confidence: 99%