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Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics
Published on: July 16, 2018
DNA Methylation Signatures of Tumor-Associated Natural Killer Cells with Self-Functionalized Nanosensor Enable
Deeptha Ishwar1,2,3,4, Krishnan Venkatakrishnan1,2,4,5, Bo Tan1,3,5
1Institute for Biomedical Engineering, Science and Technology (I BEST), Partnership between Toronto Metropolitan University and St. Michael's Hospital, Toronto, Ontario M5B 1W8, Canada.
Abstract:
Natural killer (NK) cells undergo multiple DNA genomic alterations, especially methylation-based modifications that affect activation and function. Several epigenetic modifier markers have been targeted for immunotherapy to date, but the possibility of cancer diagnosis using NK cell's DNA has been overlooked. Here, we investigated the potential use of NK cell DNA genome modifications as markers for the diagnosis of colorectal cancer (CRC) and validated their efficacy in CRC patients. Using Raman spectroscopy as the detection methodology, we identified CRC-specific methylation signatures by comparing CRC-interacted NK cells to healthy circulating NK cells. Subsequently, we identified methylation-dependent alterations in these NK cell populations. These markers were then utilized by a machine learning algorithm to develop a diagnostic model with predictive capabilities. The diagnostic prediction model accurately differentiated CRC patients from normal controls. Our findings demonstrated the utility of NK DNA markers in the diagnosis of CRC.
Insights
Researchers explored DNA methylation in natural killer (NK) cells for colorectal cancer (CRC) diagnosis. This study identified specific NK cell DNA markers for early CRC detection, offering a novel diagnostic approach.
Area of Science:
- Immunology
- Genomics
- Cancer Research
Background:
- Natural killer (NK) cells play a crucial role in immune surveillance and are known to undergo DNA alterations, including methylation.
- Epigenetic modifications in NK cells can impact their function and activation, presenting potential biomarkers.
- While NK cell-based immunotherapies are established, their DNA has been largely overlooked for cancer diagnostics.
Purpose of the Study:
- To investigate the potential of NK cell DNA genomic modifications as diagnostic markers for colorectal cancer (CRC).
- To validate the efficacy of these NK cell DNA markers in differentiating CRC patients from healthy individuals.
- To establish a predictive diagnostic model for CRC using NK cell DNA signatures.
Main Methods:
- Utilized Raman spectroscopy for the detection of DNA methylation signatures in NK cells.
- Compared NK cells from CRC patients with those from healthy controls to identify CRC-specific methylation patterns.
- Employed a machine learning algorithm to develop a diagnostic model based on identified NK cell DNA markers.
Main Results:
- Identified specific methylation signatures in NK cells associated with colorectal cancer.
- Detected methylation-dependent alterations in NK cell DNA unique to CRC patients.
- Developed a predictive diagnostic model that accurately distinguished CRC patients from healthy controls.
Conclusions:
- NK cell DNA modifications serve as viable biomarkers for colorectal cancer diagnosis.
- The developed diagnostic model demonstrates high accuracy in identifying CRC.
- This research highlights a novel, non-invasive approach for CRC detection using NK cell genomics.

