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Detection of colorectal cancer

A technology for colorectal cancer and subjects, applied in the field of colorectal cancer treatment, colorectal cancer screening, and colorectal cancer screening, can solve the problems of insufficient colorectal cancer screening technology

Pending Publication Date: 2022-03-01
UNIVERSAL DIAGNOSTICS SL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Statistics Show Current Colorectal Cancer Screening Technology Is Not Enough

Method used

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  • Detection of colorectal cancer
  • Detection of colorectal cancer
  • Detection of colorectal cancer

Examples

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Embodiment 1

[0253] Example 1. Identification of methylation biomarkers associated with colorectal cancer

[0254] This example includes the identification of one or more CpG loci that are hypermethylated in colon and rectal cancer compared to healthy controls. In particular, the experiments of this example examined CpG methylation in samples from (i) colon cancer in 341 subjects previously diagnosed with colon cancer who had not previously received chemotherapy therapy or radiotherapy; (ii) rectal cancer in 118 subjects previously diagnosed with rectal cancer who had not previously received chemotherapy or radiotherapy; (iii) 40 subjects not diagnosed with rectal cancer Colon of healthy control subjects with colorectal cancer; (iv) leukocytes of 10 healthy control subjects not diagnosed with colorectal cancer. Tissue samples were fresh frozen tissue.

[0255]Samples were analyzed for DNA methylation by a global methylomics analysis platform (Infinium HumanMethylation450 (HM450) bead tes...

Embodiment 2

[0258] Example 2: Development of a cell-free DNA assay for methylation biomarkers by MSRE-qPCR

[0259] This example develops a circulating cell-free DNA (cfDNA)-based assay to determine the methylation status of colorectal cancer methylation biomarkers. cfDNA is incomplete and fragmented, and the mechanism by which cfDNA is transported from cancer cells to the blood (as part of it called circulating tumor DNA) is unknown. At least because the 253 methylation biomarkers of Example 1 were identified from tissue samples, it was not known prior to the experiments of this Example whether the identified colorectal cancer methylation biomarkers could be adequately analyzed from cfDNA to Successful capture of ctDNA fractions allows identification of subjects or samples of colorectal cancer.

[0260] As a critical step in determining whether the colorectal cancer methylation biomarkers identified in Example 1 can be adequately analyzed from cfDNA to successfully capture the fraction ...

Embodiment 3

[0266] Example 3: MSRE-qPCR of cfDNA successfully differentiated subjects by colorectal cancer status

[0267] To probe the clinical diagnostic and prognostic capabilities of the identified methylated biomarkers, MSRE-qPCR oligonucleotides covering 180 methylated biomarker sites were tested in cfDNA extracted from the plasma of human subjects Acid primer pairs amplify the DMR, and appropriate controls. Subjects were undiagnosed individuals seeking or receiving a diagnosis of probable colorectal cancer, allowing methylation biomarker analysis to be performed prior to conventional colorectal cancer diagnostic testing and then compared to subsequent conventional diagnoses. In particular, cfDNA was obtained from undiagnosed individuals seeking or being obtained at screening centers and oncology clinics in Spain and the United States between 2017 and 2018 for a possible colorectal cancer diagnosis. The first subject group included 70 such individuals (see figure 2 description of...

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Abstract

The present disclosure provides, inter alia, methods for colorectal cancer screening and compositions related thereto. In various embodiments, the present disclosure provides methods for colorectal cancer screening comprising analyzing the methylation status of one or more methylation biomarkers, as well as compositions related thereto. In various embodiments, the present disclosure provides a method for colorectal cancer screening that includes screening for the methylation status of one or more methylation biomarkers in cfDNA, e.g., in ctDNA. In various embodiments, the present disclosure provides a method for colorectal cancer screening, comprising screening the methylation status of one or more methylation biomarkers in cfDNA, e.g., in ctDNA, using MSRE-qPCR.

Description

Background technique [0001] Cancer screening is an important part of cancer prevention, diagnosis and treatment. According to some reports, colorectal cancer (CRC) has been identified as the third most common cancer type and the second most frequent cause of cancer death in the world. According to some reports, there are more than 1.8 million new cases of colorectal cancer and about 881,000 deaths from colorectal cancer each year, accounting for about one-tenth of all cancer deaths. Regular colorectal cancer screening is recommended, especially for individuals over the age of 50. Furthermore, the incidence of colorectal cancer in individuals under the age of 50 increases over time. Statistics show that current screening techniques for colorectal cancer are inadequate. Contents of the invention [0002] Despite improvements over time, only about 40% to 44% of colorectal cancers are currently detected by early, localized-stage screening. This is at least in part due to ins...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6886C12Q1/686C12N15/11
CPCC12Q1/6886C12Q1/686C12Q2600/112C12Q2600/154
Inventor M·比滕茨K·克鲁斯马J·马丁内兹-巴雷亚C·亨塞M·切西科拉P·科纳普
Owner UNIVERSAL DIAGNOSTICS SL
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