Gene Expression Classifier for Lung Cancer Risk Assessment

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Solution Overview

Problem

Early-stage lung cancer diagnosis is challenging due to the difficulty in accessing peripheral lung airway lesions with standard techniques like bronchoscopy, and existing methods often provide indeterminate or non-diagnostic results.

Innovation Solution

A method involving gene expression analysis of mRNA from biological samples using informative genes and genomic correlate genes to assess lung cancer risk, which includes determining mRNA expression levels of specific genes related to lung cancer status and self-reportable characteristics like smoking and age, and generating a lung cancer risk assessment using a classifier.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If standard bronchoscopy techniques are used to access peripheral lung airway lesions, then the procedure is minimally invasive, but the ability to obtain diagnostic cells is poor

Engineering Contradiction:
Improveminimally invasive procedureVSAvoiddiagnostic accuracy
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent uses gene expression profiles as an intermediary to bridge the gap between non-diagnostic bronchoscopy results and accurate cancer detection. By analyzing the molecular signature of cells obtained during bronchoscopy (even when morphologically normal), the system provides diagnostic information without requiring additional invasive procedures to access peripheral lesions.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical limitation of visual and tactile detection during bronchoscopy with molecular analysis. Instead of relying on direct observation or biopsy of peripheral lesions (which are difficult to reach), the system uses gene expression profiling to detect cancer status, substituting mechanical access requirements with biochemical detection capabilities.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

2Measurement precision

If more invasive procedures are used to access peripheral lung lesions, then diagnostic accuracy improves, but patient risk and procedure complexity increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidprocedure complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent performs diagnostic analysis in advance by profiling gene expression from cells obtained during routine bronchoscopy. This preliminary molecular characterization allows clinicians to assess lung cancer risk before pursuing more invasive procedures, potentially avoiding unnecessary complex interventions while maintaining high diagnostic accuracy.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

Gene expression profiling serves as an intermediary that provides diagnostic information without requiring direct visualization or biopsy of peripheral lesions. This molecular mediator enables accurate cancer detection while avoiding the increased complexity and risk associated with more invasive procedural approaches.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Measurement precision

If gene expression analysis of multiple genes is performed, then diagnostic accuracy improves, but analysis complexity and cost increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidanalysis complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent segments the diagnostic task into two functional components: (1) obtaining cells during routine bronchoscopy (which is already being performed), and (2) analyzing specific gene expression profiles. This segmentation allows the complex diagnostic problem to be solved by adding molecular analysis to an existing procedure rather than creating entirely new complex diagnostic systems.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent makes the existing bronchoscopy procedure multi-functional by adding gene expression profiling capability. The same cells obtained for routine diagnostic purposes are also used for molecular characterization, enabling the procedure to serve both traditional diagnostic and cancer detection functions without requiring separate complex analytical systems.

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

Data Source

PatentEP3169814B1Methods for evaluating lung cancer status
Publication Date: 2022.05.04 VERACYTE INC
  • EP3169814B1 patent drawingFigure 1
  • EP3169814B1 patent drawingFigure 2
  • EP3169814B1 patent drawingFigure 3

AI summary

The disclosure in some aspects provides methods of determining the likelihood that a subject has lung cancer based on the expression of informative-genes. In other aspects, the disclosure provides methods for determining an appropriate diagnostic intervention plan for a subject based on the expression of informative-genes. Related compositions and kits are provided in other aspects of the disclosure.