CAGE Analysis for Endometrial Cancer Metastasis Assessment
Solution Overview
Problem
Current methods lack a reliable approach to differentiate between endometrial cancer with lymph node metastasis and without metastasis, often resulting in unnecessary lymph node dissection and associated complications.
Innovation Solution
The method involves comprehensive analysis of RNA expression near transcription start sites using CAGE analysis to identify specific transcription start sites and markers, such as TACC2, to assess lymph node metastatic potential in endometrial cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If lymph node dissection is performed to confirm metastasis, then accurate diagnosis of lymph node metastatic potential is achieved, but unnecessary dissection and associated complications occur
Solution Approach 1:
The patent applies preliminary action by performing CAGE analysis on cancer tissue samples obtained before lymph node dissection to assess lymph node metastatic potential. This preliminary molecular analysis identifies patients at high risk of metastasis, allowing surgeons to proceed with dissection only when necessary, thereby avoiding unnecessary surgical complications while maintaining diagnostic accuracy.
Solution Approach 2:
The patent introduces an intermediary approach by using CAGE analysis and specific gene expression markers (such as TACC2, BIRC5, and MYC) as intermediate indicators of lymph node metastatic potential. These molecular markers serve as mediators between the primary tumor characteristics and the actual metastatic status, providing a non-invasive assessment method that reduces the need for exploratory lymph node dissection.
2Object-affected harmful factors
If lymph node dissection is avoided to reduce complications, then surgical morbidity decreases, but accurate assessment of metastatic potential is lost
Solution Approach 1:
The patent replaces the mechanical surgical approach (lymph node dissection) with a molecular analysis system based on CAGE analysis and gene expression profiling. This substitution allows accurate assessment of lymph node metastatic potential through biochemical markers (such as TACC2, BIRC5, MYC expression levels) without requiring physical removal and pathological examination of lymph nodes, thereby reducing surgical morbidity while maintaining assessment precision.
Solution Approach 2:
The patent changes the assessment parameters from macroscopic surgical parameters (presence/absence of metastatic cells in dissected nodes) to molecular parameters (gene expression levels, transcription start site activity). By measuring expression levels of specific genes and transcriptional activity in the primary tumor tissue, the system provides precise metastatic potential assessment without the need for lymph node dissection, thus reducing surgical morbidity.
3Measurement precision
If comprehensive gene expression analysis is performed to identify metastatic markers, then discrimination accuracy improves, but analysis complexity increases
Solution Approach 1:
The patent extracts and focuses on specific, high-value targets from the comprehensive gene expression data obtained by CAGE analysis. Instead of analyzing all genes, the method identifies and measures expression levels of specific metastatic markers (such as TACC2, BIRC5, MYC) and transcription start sites that have been shown to correlate with lymph node metastatic potential. This extraction approach maintains high discrimination accuracy while significantly reducing analysis complexity compared to whole-genome analysis.
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 allows for accurate discrimination between endometrial cancer with and without lymph node metastasis, reducing the need for unnecessary lymph node dissection and associated complications like postoperative lymphedema, and provides an objective classification equivalent to clinical specialists.
Implementation Method 1
CAGE (cap analysis gene expression; Non Patent Literature 2) are known to comprehensively analyze the expression statuses of genes at transcription start sites as sequence information. Of these methods, CAGE is characterized in that this method is capable of comprehensively quantifying the activity of transcription start points by selecting long capped RNAs such as mRNA and sequencing their 5' ends at random and at a large scale.
Implementation Method 2
RNA-seq (Non Patent Literature 1) and CAGE (cap analysis gene expression; Non Patent Literature 2) are known to comprehensively analyze the expression statuses of genes at transcription start sites as sequence information.
Implementation Method 3
the testing kit comprising an oligonucleotide specifically hybridizing to a transcription product of the DNA
Data Source
Figure 1~2
AI summary
Provided is an approach for discriminating endometrial cancer at a molecular level between endometrial cancer with lymph node metastasis and that without metastasis. A method for assessing lymph node metastasis or lymph node metastatic potential of endometrial cancer, comprising the step of measuring an expression level of an expression product of at least one DNA comprising a transcription start site in a biological sample derived from a cancer tissue isolated from an endometrial cancer patient, wherein the DNA comprises a base at an arbitrary position in the transcription start site in any of nucleotide sequences represented by SEQ ID NOs: 1 to 277 and at least one or more bases located immediately downstream thereof, and the transcription start site is a region wherein both ends thereof are defined by the first base in any of the nucleotide sequences represented by SEQ ID NOs: 1 to 277 and the 101st base counted from the 3' end.