ACTN4 Gene Amplification Detection for Breast Cancer Prognosis

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Solution Overview

Problem

Current methods for predicting breast cancer prognosis, particularly those using the proportion of Ki67 positive cells and ACTN4 gene amplification, are not accurate and lack clinical recognition, failing to establish a reliable link between ACTN4 gene amplification and prognosis.

Innovation Solution

A method and apparatus that detect copy number increase and gene amplification of the ACTN4 gene in biological samples from breast cancer patients, specifically those who are HER2 negative, hormone receptor positive, and lymph node metastasis negative, to predict prognosis by measuring the copy number of ACTN4 gene per cell and its amplification ratio to the centromere of chromosome 19, using techniques like FISH and quantitative PCR.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If the proportion of Ki67 positive cells is used as the only prognosis predictive factor, then the method is simple to implement, but the prognosis prediction accuracy is insufficient

Engineering Contradiction:
Improvesimplicity of prognosis prediction methodVSAvoidprognosis prediction accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent combines multiple prognosis predictive factors (Ki67 protein expression, ACTN4 gene amplification status, and hormone receptor status) into a unified prediction system. This integration allows the method to maintain operational simplicity while significantly improving prognosis prediction accuracy by considering multiple biomarkers simultaneously rather than relying on a single factor.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The patent develops a multi-functional prognosis prediction method that can evaluate multiple aspects of breast cancer prognosis through a single comprehensive assessment. The method simultaneously evaluates cell proliferation (Ki67), gene amplification (ACTN4), and hormone receptor status, providing universal applicability across different prognostic scenarios while maintaining ease of operation.

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Measurement precision

If ACTN4 gene amplification is used as a prognosis predictive marker, then the prognosis prediction accuracy is improved, but the clinical recognition and validation are insufficient

Engineering Contradiction:
Improveprognosis prediction accuracyVSAvoidclinical recognition and validation
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent applies local quality by specifically targeting ACTN4 gene amplification at the 19q13.1 locus in breast cancer cells. This localized approach focuses on a specific genomic region known to be associated with poor prognosis, providing clinically relevant and validated information that enhances both prediction accuracy and clinical recognition.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent performs preliminary validation of ACTN4 gene amplification as a prognosis predictive marker through comprehensive clinical studies and correlation analyses. By establishing the reliability of this marker in advance through rigorous validation, the method ensures both high prediction accuracy and strong clinical recognition before implementing the prognosis prediction system.

Inventive Principle:
Principle #10Preliminary action

3Measurement precision

If only gene amplification detection is performed, then the prognosis prediction is more specific, but the amount of ACTN4 protein expression is less useful as a marker

Engineering Contradiction:
Improveprognosis prediction specificityVSAvoidusefulness of ACTN4 protein amount
Core Design Contradiction:
Measurement precisionVSQuantity of substance

Solution Approach 1:

The patent extracts and focuses on the gene amplification status of ACTN4 as the primary prognostic indicator, separating this specific genetic feature from the overall protein expression analysis. By isolating the gene amplification detection as the key predictive factor, the method achieves higher prognosis prediction specificity while acknowledging that protein amount alone is less useful, thus resolving the contradiction between specificity and substance quantity.

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentEP3293273B1Method for assisting judgment of prognosis of breast cancer, and apparatus for assisting judgment of prognosis of breast cancer
Publication Date: 2020.11.04 SYSMEX CORP
  • EP3293273B1 patent drawingFigure 1~2
  • EP3293273B1 patent drawingFigure 3A~3B
  • EP3293273B1 patent drawingFigure 4

AI summary

Disclosed is a method for assisting the judgment of the prognosis for a patient with breast cancer, the method comprising the steps of: detecting ACTN4 gene contained in a biological sample of the patient; and judging that the prognosis of breast cancer is poor if at least one selected from the group consisting of the copy number increase of ACTN4 gene and the gene amplification of ACTN4 gene is present; wherein the patient is HER2 negative, hormone receptor positive and lymph node metastasis negative.