Colorectal Cancer EPIS/TMES Scores for Tumor Compartment Stratification

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current prognostic strategies for colorectal cancer (CRC) primarily rely on tumor staging, histopathological analysis, and molecular biomarkers like KRAS, NRAS, and BRAF mutations, but fail to fully account for the influence of the tumor microenvironment (TME), leading to suboptimal therapeutic strategies and patient outcomes.

Innovation Solution

Development of 10-gene tumor microenvironment signature (TMES) and 10-gene epithelial signature (EPIS) scores to quantify the contributions of tumor epithelium and TME, guiding targeted therapies such as immunotherapy, EGFR inhibitors, and MEK inhibitors based on gene expression levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current prognostic strategies relying on tumor staging and molecular biomarkers are used, then therapeutic decisions can be made, but the influence of tumor microenvironment is not fully accounted for, leading to suboptimal treatment outcomes

Engineering Contradiction:

Improveprognostic accuracyVSAvoidtumor microenvironment contribution

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent segments the tumor tissue into two distinct components: tumor epithelium and tumor microenvironment. By developing separate gene signatures (EPIS for epithelium, TMES for microenvironment) and calculating independent scores for each component, the method captures the distinct prognostic contributions of both compartments, resolving the information loss about TME influence while maintaining reliable prognosis

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent introduces gene expression signatures as intermediary markers that mediate between the complex tumor biology and clinical decision-making. The EPIS and TMES scores serve as quantitative intermediaries that translate molecular profiles into actionable prognostic information, enabling integration of TME influence without requiring direct observation of complex cellular interactions

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If comprehensive tumor microenvironment analysis is implemented, then better patient stratification and treatment optimization are achieved, but the complexity of the analytical framework increases

Engineering Contradiction:

Improvepatient stratification accuracyVSAvoidanalytical framework complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The complex analytical framework is segmented into two independent but complementary analysis streams: one for epithelial genes (EPIS) and one for microenvironment genes (TMES). Each stream processes specific gene sets independently and produces separate scores, which can then be integrated. This segmentation reduces analytical complexity while maintaining comprehensive patient stratification capability

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates a universal prognostic framework that can be applied across different CRC patient populations and treatment contexts. The dual-score system (EPIS and TMES) serves multiple functions: risk stratification, treatment response prediction, and therapeutic decision support, making the system versatile without proportionally increasing complexity

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250305059A1Predictive biomarkers in colorectal cancer

Publication Date: 2025.10.02 UNIV OF SOUTH FLORIDA

AI summary

Disclosed herein are methods and compositions for quantifying distinct prognostic and predictive contributions of tumor epithelium vs. tumor microenvironment in colorectal cancer to optimize therapy.