Gene Expression Analysis for Thyroid Nodule Diagnosis
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Solution Overview
Problem
Current diagnostic methods for thyroid nodules, particularly fine-needle aspiration biopsy (FNAB), face challenges in accurately distinguishing between benign and malignant thyroid nodules due to insufficient or low-quality nucleic acid samples, leading to a high rate of indeterminate results and unnecessary surgeries.
Innovation Solution
A method utilizing a set of specific genes, including C3, CAMK2N1, DUSP5, EGR1, EMP2, ITGA2, KCNQ3, MET, METTL7B, MPZL2, PSD3, SDC4, SLC26A4, SLPI, TM4SF1, TPO, SLC26A7, and TUSC3, for gene expression analysis in FNAB samples, combined with a classifier algorithm, to determine the malignant character of thyroid nodules based on RNA expression levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If fine-needle aspiration biopsy (FNAB) is used for thyroid nodule diagnosis, then the diagnostic procedure is minimally invasive and can be performed easily, but the amount of material obtained is insufficient for comprehensive analysis leading to indeterminate results
Solution Approach 1:
The invention extracts and concentrates nucleic acids from the limited FNAB material through systematic extraction procedures, separating the diagnostic information (nucleic acids) from the insufficient sample volume. This allows comprehensive molecular analysis despite the small initial sample size.
Solution Approach 2:
The invention combines multiple diagnostic approaches (cytological evaluation, molecular diagnostics, and gene expression analysis) into an integrated diagnostic system. By merging these methods, the system overcomes the limitations of individual approaches and achieves accurate diagnosis from minimal material.
2Measurement precision
If more genes are analyzed for thyroid nodule diagnosis, then the diagnostic accuracy improves, but the complexity of the diagnostic system increases
Solution Approach 1:
The invention segments the gene analysis into distinct categories: core genes (C3, CAMK2N1, DUSP5, EGR1, EMP2, ITGA2, KCNQ3, MET, METTL7B, MPZL2, PSD3, SDC4, SLC26A4, SLPI, TM4SF1, TPO, SLC26A7, TUSC3) and additional genes. This segmentation allows flexible implementation where the core set provides baseline diagnostic accuracy while additional genes can be incorporated as needed without requiring all genes to be analyzed simultaneously.
Solution Approach 2:
The invention applies different levels of analysis depth to different gene sets. The core genes are analyzed in all cases to provide fundamental diagnostic information, while additional genes are analyzed based on specific clinical needs and sample quality, creating a localized quality approach that optimizes resource allocation.
3Productivity
If FNAB material is used for multiple diagnostic purposes, then the need for additional biopsies is reduced, but the quality of nucleic acids may be insufficient for molecular analysis
Solution Approach 1:
The invention performs preliminary assessment of nucleic acid quality and quantity immediately after extraction from FNAB material. This preliminary action determines whether the sample is suitable for molecular analysis, allowing early identification of samples that will require additional processing or supplementation before committing to full molecular diagnostic workflows.
Solution Approach 2:
The invention changes the physical and chemical parameters of the FNAB material through systematic nucleic acid extraction and concentration procedures. By transforming the sample from a cellular suspension to purified nucleic acid preparations with optimized concentration and purity, the material becomes suitable for multiple diagnostic applications including molecular diagnostics and gene expression analysis.
Data Source
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AI summary
A method of testing genes for diagnosing thyroid nodules in an unspecified sample from biopsy (FNAB) material, from which RNA is isolated, then RNA upon transcription is synthesized into cDNA, followed by determination and normalization of gene expression. The material is a frozen or a freshly collected residual biopsy (washout needle) from washing the residue in the bevel of the needle, containing RNA at a concentration ranging from 4 ng/µl to 20 ng/µl, which is pre-amplified before transcription of total RNA at a number of cycles depending on RNA concentration. The length of the obtained gene amplicons ranges between 53base pairs and 134 base pairs. In addition, the expression of genes selected from transcription factors of the corresponding target gene is analyzed, and the normalization of expression of target genes is carried out under endogenous control of at least four normalizing genes, preferably six normalizing genes. The use of genes from the set including C3, CAMK2N1, DUSP5, EGR1, EMP2, FAM20A, FAXC, ITGA2, KCNQ3, MET, METTL7B, MPZL2, PSD3, SDC4, SLC26A4, SLPI, TM4SF1, TPO, SLC26A7, and TUSC3, for diagnosing of thyroid nodules in an ultra-small residual biopsy sample or full biopsy with RNA concentrations ranging from 4 ng/µl to 20 ng/µl. (10 claims)