Compositions and methods for detecting sessile serrated adenomas/polyps
Inventors
GLAZKO, Galina • Hagedorn, Curt H. • RAHMATALLAH, Yasir
Assignees
US Department of Veterans Affairs • BioVentures LLC
Publication Number
US-11236398-B2
Publication Date
2022-02-01
Expiration Date
2038-03-01
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Abstract
The disclosure provides a method to detect sessile serrated adenomas/polyps (SSA/Ps) and to differentiate SSA/Ps from hyperplastic polyps (HPs). The method uses a molecular signature that is platform-independent and could be used with multiple platforms such as microarray, RNA-seq or real-time quantitative platforms.
Core Innovation
The invention provides methods and compositions for detecting sessile serrated adenomas/polyps (SSA/Ps) and for differentiating SSA/Ps from hyperplastic polyps (HPs) using a molecular signature. This molecular signature is platform-independent and applicable across multiple platforms such as microarray, RNA-seq, or real-time quantitative PCR (qPCR), thereby enabling reliable detection and classification of these colonic lesions.
Colon cancer, a leading cause of cancer-related deaths, arises from polyps in the colon that develop along distinct pathways, including the serrated pathway. SSA/Ps, a subset of serrated polyps previously misclassified as HPs, account for approximately 20-30% of colon cancers due to their malignant potential. Differentiating SSA/Ps from HPs is challenging using current histopathological approaches due to overlapping morphological features, leading to misclassification and inappropriate patient follow-up or treatment.
The disclosure addresses the need for a reliable diagnostic assay to aid in distinguishing SSA/Ps from HPs. It provides molecular signatures comprising specific nucleic acids whose expression levels differ between SSA/Ps and HPs, allowing accurate detection and differentiation. This improved accuracy, demonstrated to be approximately 90% even on formalin-fixed paraffin-embedded (FFPE) tissues, facilitates appropriate treatment decisions such as more aggressive management and surveillance, potentially reducing colorectal cancer incidence and mortality.
Claims Coverage
The patent document contains one independent claim directed to a method for detecting a sessile serrated adenoma/polyp (SSA/P) in a subject, comprising molecular expression profiling steps and treatment.
Molecular signature comprising specific nucleic acids for SSA/P detection
The method determines the expression levels of a molecular signature consisting of nucleic acids CHFR, CHGA, CLDN1, KIZ, MEGF6, NTRK2, PLA2G16, PTAFR, SBSPON, SMEG1, SLC7A9, SPIRE1, and TACSTD2, with the optional inclusion of FOXD1, PIK3R3, PRUNE2, TPD52L1, TRIB2, C4BPA, CPE, DPP10, GRAMD1B, GRIN2D, KLK7, MYNC, TM4SF4 and normalization controls.
Comparative expression analysis against reference value
The method compares the level of expression of each nucleic acid in the molecular signature to a reference expression level set by non-diseased or hyperplastic polyp samples to detect SSA/Ps.
Detection criteria for SSA/P presence
SSA/P detection is defined by decreased expression of CHFR, CHGA, and NTRK2 and increased expression of CLDN1, KIZ, MEGF6, PLA2G16, PTAFR, SBSPON, SMEG1, SLC7A9, SPIRE1, and TACSTD2 relative to the reference.
Treatment following detection
Upon detection of SSA/Ps, the method includes removing the SSA/P by methods selected from polypectomy, endoscopic resection, and surgical resection.
The claims primarily cover a method for detecting SSA/Ps using a defined molecular signature measuring nucleic acid expression in a subject's biological sample, comparing to reference expression levels, applying specific expression change criteria to detect SSA/Ps, and subsequently treating the detected SSA/P by resection. The claimed molecular signature and the detection method provide a platform-independent, accurate diagnostic tool guiding patient management.
Stated Advantages
Provides an accurate, reliable assay that distinguishes sessile serrated adenomas/polyps from hyperplastic polyps with approximately 90% accuracy, even from FFPE tissue samples.
The molecular signature is platform-independent, allowing use across microarray, RNA-seq, and real-time qPCR platforms.
Supports improved diagnosis and surveillance stratification of patients, enabling earlier and more appropriate treatment and reducing colorectal cancer risk.
Documented Applications
Detecting sessile serrated adenomas/polyps (SSA/Ps) in subjects.
Differentiating SSA/Ps from hyperplastic polyps (HPs) to improve diagnostic accuracy.
Predicting the likelihood that colorectal polyps will develop into colorectal cancer based on molecular signature expression patterns.
Determining treatment strategies for subjects diagnosed with or suspected of having serrated polyps, including more aggressive intervention if SSA/Ps are detected.
Monitoring serrated polyps over time in a subject to assess disease progression or response to treatment.
Utilizing kits comprising detection agents for the expression products of the molecular signature for diagnostic and therapeutic selection purposes.
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