Noncoding RNA Biomarkers for KRAS Mutation Detection

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Solution Overview

Problem

Current methods for detecting RAS pathway mutations, particularly in cancers like lung cancer, are inadequate in utilizing noncoding RNA expression levels for early diagnosis and treatment, as they fail to comprehensively assess the impact of oncogenic RAS signaling on the noncoding transcriptome.

Innovation Solution

The method involves obtaining a biological sample, isolating nucleic acids, and analyzing the expression levels of noncoding RNAs in conjunction with a control sample to identify differential expression indicative of RAS pathway mutations, using techniques such as PCR, RT-PCR, and RNA-sequencing to determine the presence of mutations in genes like KRAS, and administering anticancer agents based on the analysis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current methods for detecting RAS pathway mutations are used, then detection can be performed, but they fail to comprehensively assess the impact of oncogenic RAS signaling on the noncoding transcriptome

Engineering Contradiction:

Improvedetection accuracyVSAvoidnoncoding transcriptome information

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The method analyzes multiple types of RNA molecules (coding and noncoding RNAs) simultaneously to provide a comprehensive assessment of RAS pathway mutations. This multi-functional approach enables detection of mutations while also evaluating their impact on the broader transcriptome, including long noncoding RNAs, microRNAs, and circular RNAs.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention extends detection beyond traditional protein-coding gene analysis to include the noncoding RNA dimension. By measuring expression levels of noncoding RNAs alongside coding RNAs, the method adds a new dimension of information that reveals the functional impact of RAS pathway mutations on gene regulation and cellular processes.

Inventive Principle:

Principle #17Another dimension (Dimensionality change)

2Reliability

If expression levels of multiple noncoding RNAs are analyzed, then comprehensive detection of RAS pathway mutations is achieved, but measurement complexity increases

Engineering Contradiction:

Improvedetection reliabilityVSAvoidmeasurement system complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The method combines multiple RNA analysis measurements into a unified diagnostic approach. By simultaneously measuring expression levels of various noncoding RNAs (lncRNAs, microRNAs, circular RNAs) and coding RNAs using integrated techniques such as RNA-sequencing or microarrays, the system achieves reliable mutation detection while managing complexity through consolidation of measurement protocols.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention uses differential expression patterns of noncoding RNAs as intermediary markers to infer the presence and impact of RAS pathway mutations. These noncoding RNA expression profiles serve as mediators that translate complex molecular changes into detectable diagnostic signals, simplifying the interpretation of comprehensive transcriptome data.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Loss of time

If noncoding RNA expression analysis is performed to enable early detection, then diagnostic capability is improved, but analysis time and resource requirements increase

Engineering Contradiction:

Improvediagnosis timeVSAvoidanalysis throughput

Core Design Contradiction:

Loss of timeVSProductivity

Solution Approach 1:

The method performs preliminary analysis of noncoding RNA expression profiles to identify characteristic patterns associated with RAS pathway mutations before comprehensive clinical evaluation. By establishing baseline expression levels and detecting early differential changes, the system enables earlier diagnosis while streamlining subsequent analysis steps to maintain productivity.

Inventive Principle:

Principle #10Preliminary action

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 early detection of RAS pathway mutations by analyzing noncoding RNA expression, facilitating targeted therapy with inhibitors, thereby improving cancer diagnosis and treatment outcomes.

Implementation Method 1

measuring the expression level of the one or more genes comprises performing polymerase chain reaction (PCR)

Methodology Applied

Scientific EffectPolymerase chain reaction (PCR):

Implementation Method 2

measuring the expression level of the one or more genes comprises performing reverse transcriptase polymerase chain reaction (RT-PCR)

Methodology Applied

Scientific EffectReverse transcriptase polymerase chain reaction (RT-PCR):

Data Source

PatentUS20230340606A1Extracellular repetitive RNA biomarkers of mutant KRAS cancers

Publication Date: 2023.10.26 RGT UNIV OF CALIFORNIA

AI summary

The disclosure provides methods for detecting a RAS pathway mutation in a subject. The methods include obtaining a biological sample from the subject, isolating nucleic acids from the biological sample, and analyzing the expression level of noncoding RNAs in the nucleic acids in conjunction with a corresponding reference level in a control sample, wherein a differential expression level of the noncoding RNAs compared to the corresponding reference level in the control sample indicates that the subject has a RAS pathway mutation.