Methods to assess the likelihood of dysplasia or esophageal adenocarcinoma

A technology for dysplasia and esophageal adenocarcinoma, applied in biochemical equipment and methods, microbial determination/inspection, etc., can solve the problem of not providing biomarkers, and achieve the effect of overcoming sampling bias

Active Publication Date: 2015-04-08
英国研究与创新署
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No specific teaching on biomarkers or prognosis is provided in this document

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  • Methods to assess the likelihood of dysplasia or esophageal adenocarcinoma
  • Methods to assess the likelihood of dysplasia or esophageal adenocarcinoma
  • Methods to assess the likelihood of dysplasia or esophageal adenocarcinoma

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Embodiment Construction

[0059] We taught that DNA methylation can detect insignificant dysplasia and early tumors in Barrett's esophagus, DNA methylation detects dysplasia / cancer.

[0060] Changes in the methylation of specific genes may be ideal biomarkers since physiological inactivation of one allelic copy already occurs in females by imprinting and by X-inactivation.

[0061] We performed DNA methylation screens of BE and EAC samples using the array to determine candidate biomarkers. We analyzed imprinted and X-chromosome genes separately and purposefully separated males from females to allow meaningful conclusions to be drawn. We performed robust internal and external validation using pyrosequencing, which is currently the gold standard in DNA methylation analysis, and from which a panel of biomarkers could be determined to distinguish dysplastic from non-dysplastic BE. Finally, we validated the biomarker panel with real-time analysis in a prospective cohort to stratify BE patients into low, in...

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Abstract

In some embodiments, a method for aiding assessment of the likelihood of dysplasia or esophageal adenocarcinoma being present in a subject can include (a) providing an esophagal sample from said subject (b) determining the methylation status of (i) SLC22A18, (ii) PIGR, (iii) GJA12 and (iv) RIN2 in said sample wherein if 2 or more of said genes are methylated then an increased likelihood of presence of dysplasia or esophageal is determined. The invention also relates to apparatus for same.

Description

Background technique [0001] Patients with Barrett's esohphagus (BE) have a substantially increased risk of progression to esophageal adenocarcinoma (EAC) compared to the general population (RR: 11.3, 95% CI: 8.8-14.4) 1 . The incidence of EAC has increased 7-fold (3.6 to 25.6 cases per million) over the past 30 years2 and its prognosis is poor due to late manifestations, with a median survival of approximately 11 months3. Due to the increased survival of diagnosed patients when the disease is confined to the mucosa or sub-mucosa layers; patients with BE are recommended to undergo endoscopic surveillance for early detection of cancer4,5. The cost-effectiveness and risk:benefit ratio for patients with endoscopy has been repeatedly questioned because the annual (yearly) risk of progression is relatively low; The intermediate dysplastic stage between BE and EAC is the most reliable marker of progression; however, the presence of pathological dysplasia is subjective due to known s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCC12Q2600/154C12Q1/6886
Inventor 丽贝卡·菲茨杰拉德穆罕默德·阿尔维新学·刘
Owner 英国研究与创新署
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