cfDNA Methylation Panel for Early Ovarian Cancer Detection
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Solution Overview
Problem
Current methods for diagnosing ovarian cancer, particularly epithelial ovarian cancer (EOC), are inadequate for early detection due to low sensitivity and specificity, and existing serum biomarkers like CA125 and HE4 have limited effectiveness, while transvaginal ultrasound is inconvenient and time-consuming, leading to a high mortality rate from late-stage diagnoses.
Innovation Solution
A diagnostic panel using cell-free DNA (cfDNA) methylation markers, including OV1, OV2, OV3, OV4, OV5, OV6, OV7, OV8, OV9, OV10, OV11, OV12, OV13, OV14, OV15, OV16, OV17, OV18, OV19, OV20, and OV21, analyzed with bisulfite treatment and nucleic acid amplification, combined with an AI algorithm for pattern recognition, to identify aberrant methylation patterns indicative of EOC.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If serum biomarker CA125 is used for EOC detection, then the test is simple and inexpensive, but the sensitivity is low leading to late diagnosis
Solution Approach 1:
The patent combines multiple cfDNA methylation markers (OV1, OV2, OV3, OV4, OV5, OV6, OV7, OV8, OV9, OV10, OV11, OV12, OV13, OV14, OV15, OV16, OV17, OV18, OV19, OV20, OV21) into a composite diagnostic panel. This merging of multiple markers achieves high sensitivity (84.15% when combined with CA125) while maintaining operational simplicity through a single blood draw and standardized laboratory processing.
2Measurement precision
If transvaginal ultrasound is used for EOC detection, then the sensitivity and accuracy are high, but the procedure is inconvenient and time-consuming
Solution Approach 1:
The patent replaces the mechanical transvaginal ultrasound procedure with an in vitro biochemical analysis system. Instead of using ultrasound waves and manual sonographer interpretation, the invention uses automated cfDNA extraction, bisulfite treatment, and methylation marker analysis from a simple blood sample, eliminating the need for specialized equipment and trained sonographers while maintaining high detection accuracy.
3Measurement precision
If cfDNA methylation analysis is performed, then the detection sensitivity increases, but the test complexity and cost increase
Solution Approach 1:
The patent segments the complex cfDNA analysis into distinct modular steps: (1) cfDNA extraction from plasma, (2) bisulfite treatment to convert unmethylated cytosines, (3) PCR amplification of specific methylation regions, (4) sequencing or methylation-specific PCR detection. Each module can be performed independently with standardized protocols, reducing overall complexity while achieving high sensitivity through the combination of multiple methylation markers.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The method achieves high sensitivity and specificity in detecting early and late-stage EOC, improving detection rates from 60.6% to 84.15% when combined with CA125, and provides a cost-effective, time-efficient alternative to existing tests.
Implementation Method 1
Such methods can include a step of treating at least a portion of the cell-free genetic material with bisulfite
Implementation Method 2
performing an nucleic acid amplification to generate an amplification product
Data Source
AI summary
Compositions and methods for diagnosis and evaluation of prognosis of epithelial ovarian cancer (EOC) are provided. Development of an artificial intelligence approach entitled MethylBert and its application to identification of methylation sites useful in identification of EOC from cell free DNA obtained from serum or plasma is shown. PCR-based methods directed to the methylation state of the OV-1 site identified using MethylBERT approach can be used in screening for EOC using cell free DNA obtained from blood samples, and can be combined with measurement of tumor markers associated with EOC.