Gene Expression Recurrence Score Assay for Chemotherapy Prediction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current diagnostic tests for cancer, particularly breast cancer, are inadequate for predicting patient response to chemotherapy, as they are often based on single analyte measurements and subjective interpretations, lacking the ability to quantify relationships between multiple markers, and require fresh tissue samples that are not readily available.
Innovation Solution
A method for predicting the likelihood of a beneficial response to chemotherapy by quantitatively determining specific gene expression scores, including Recurrence Score, ESR1 Group Score, Invasion Group Score, Proliferation Group Threshold Score, and the expression levels of MYBL2 and SCUBE2, using RNA transcripts from formalin-fixed paraffin-embedded tissue samples, allowing for personalized treatment decisions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single analyte diagnostic tests are used, then the test is simple to perform, but it cannot capture relationships between multiple markers and provides inadequate prediction of chemotherapy response
Solution Approach 1:
The patent combines multiple gene expression markers (ESR1, PGR, BCL2, SCUBE2, CTSL2, MMP11, GRB7, ERBB2, MKI67, MYBL2, CCNB1, STK6, CD68, GSTM1, BAG1) into a single integrated Recurrence Score assay. This merging of multiple analytes into one comprehensive test enables accurate prediction of chemotherapy response while maintaining relative simplicity through a unified scoring system that integrates information from all markers.
Solution Approach 2:
The Recurrence Score is a composite diagnostic tool that integrates expression levels of multiple genes into a single predictive metric. This composite approach combines the information from diverse biological markers (hormone receptors, proliferation markers, invasion markers) to create a more robust and accurate prediction system than any single marker could provide alone.
2Measurement precision
If immunohistochemistry is used for diagnostic testing, then the method is widely available, but the results are not quantitative and vary between laboratories due to subjective interpretation
Solution Approach 1:
The patent replaces the subjective, manual interpretation process of immunohistochemistry with an automated RNA-based quantitative assay. By using RT-PCR technology to measure gene expression levels, the method eliminates human subjectivity and provides objective, quantitative results that are consistent across different laboratories while maintaining wide availability through standard molecular biology techniques.
3Measurement precision
If RNA-based tests are developed, then highly quantitative results can be obtained, but RNA is perceived to be destroyed in routinely prepared FPE tissue specimens
Solution Approach 1:
The patent converts the previously harmful effect of formalin fixation (which was thought to destroy RNA) into a beneficial opportunity by demonstrating that RNA can indeed be recovered from routinely prepared FPE tissue specimens. This approach allows the use of existing clinical archives of FPE samples for both diagnostic testing and retrospective research, transforming a limitation into an advantage by enabling quantitative RNA analysis from standard clinical specimens.
4Reliability
If fresh tissue samples are obtained for RNA analysis, then RNA quality is maintained, but it is inconvenient and often impossible to obtain and store fresh tissue samples from patients
Solution Approach 1:
The patent uses FPE tissue specimens as an intermediary medium that bridges the gap between clinical convenience and RNA quality requirements. By developing methods to extract and analyze RNA from fixed, paraffin-embedded samples, the assay eliminates the need for fresh tissue collection and storage while still achieving reliable quantitative results, thus serving as an intermediary solution that satisfies both clinical practicality and scientific rigor.
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
This approach enables accurate prediction of chemotherapy response and recurrence risk, enabling more informed treatment choices and reducing unnecessary exposure to toxic drugs by identifying patients likely to benefit from chemotherapy.
Implementation Method 1
In the past three years, it has become possible to profile gene expression of hundreds of genes in formalin-fixed paraffin-embedded (FPE) tissue using RT-PCR technology.
Data Source
AI summary
The present invention provides gene expression information useful for predicting whether a cancer patient is likely to have a beneficial response to treatment with chemotherapy, comprising measuring, in a biological sample comprising a breast tumor sample obtained from the patient, the expression levels of gene subsets to obtain a risk score associated with a likelihood of a beneficial response to chemotherapy, wherein the score comprises at least one of the following variables: (i) Recurrence Score, (ii) ESRI Group Score; (iii) Invasion Group Score; (iv) Proliferation Group Score; and (v) the expression level of the RNA transcript of at least one of MYBL2 and SCUBE2, or the corresponding expression product. The invention further comprises a molecular assay-based algorithm to calculate the likelihood that the patient will have a beneficial response to chemotherapy based on the risk score.