Rapid Detection of Cancer DNA in Human Blood Using Cysteamine-capped AuNPs and a Machine Learning-enabled Smartphone

Overview

Journal RSC Adv

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2023 Jan 23

PMID 36686949

Authors

Sireemas Koowattanasuchat

Sawinee Ngernpimai

Piyaporn Matulakul

Janpen Thonghlueng

Witthawat Phanchai

Apiwat Chompoosor

Uthumporn Panitanarak

Yupaporn Wanna

Thanapong Intharah

Kanokon Chootawiriyasakul

Pimjai Anata

Prajuab Chaimnee

Raynoo Thanan

Chadamas Sakonsinsiri

Theerapong Puangmali

Affiliations

Soon will be listed here.

Abstract

DNA methylation occurs when a methyl group is added to a cytosine (C) residue's fifth carbon atom, forming 5-methylcytosine (5-mC). Cancer genomes have a distinct methylation landscape (Methylscape), which could be used as a universal cancer biomarker. This study developed a simple, low-cost, and straightforward Methylscape sensing platform using cysteamine-decorated gold nanoparticles (Cyst/AuNPs), in which the sensing principle is based on methylation-dependent DNA solvation. Normal and cancer DNAs have distinct methylation profiles; thus, they can be distinguished by observing the dispersion of Cyst/AuNPs adsorbed on these DNA aggregates in MgCl solution. After optimising the MgCl, Cyst/AuNPs, DNA concentration, and incubation time, the optimised conditions were used for leukemia screening, by comparing the relative absorbance (Δ ). Following the DNA extraction from actual blood samples, this sensor demonstrated effective leukemia screening in 15 minutes with high sensitivity, achieving 95.3% accuracy based on the measurement by an optical spectrophotometer. To further develop for practical realisation, a smartphone assisted by machine learning was used to screen cancer patients, achieving 90.0% accuracy in leukemia screening. This sensing platform can be applied not only for leukemia screening but also for other cancers associated with epigenetic modification.

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References

Sina A, Carrascosa L, Liang Z, Grewal Y, Wardiana A, Shiddiky M . Epigenetically reprogrammed methylation landscape drives the DNA self-assembly and serves as a universal cancer biomarker. Nat Commun. 2018; 9(1):4915. PMC: 6279781. DOI: 10.1038/s41467-018-07214-w. View

Farinelli P, Perera A, Arango-Gonzalez B, Trifunovic D, Wagner M, Carell T . DNA methylation and differential gene regulation in photoreceptor cell death. Cell Death Dis. 2014; 5:e1558. PMC: 4649831. DOI: 10.1038/cddis.2014.512. View

Wee E, Ngo T, Trau M . Colorimetric detection of both total genomic and loci-specific DNA methylation from limited DNA inputs. Clin Epigenetics. 2015; 7:65. PMC: 4498563. DOI: 10.1186/s13148-015-0100-6. View

Nazmul Islam M, Yadav S, Haque M, Munaz A, Islam F, Hossain M . Optical biosensing strategies for DNA methylation analysis. Biosens Bioelectron. 2016; 92:668-678. DOI: 10.1016/j.bios.2016.10.034. View

Moradi Sarabi M, Naghibalhossaini F . Association of DNA methyltransferases expression with global and gene-specific DNA methylation in colorectal cancer cells. Cell Biochem Funct. 2015; 33(7):427-33. DOI: 10.1002/cbf.3126. View

Su F, Wang L, Sun Y, Liu C, Duan X, Li Z . Highly sensitive detection of CpG methylation in genomic DNA by AuNP-based colorimetric assay with ligase chain reaction. Chem Commun (Camb). 2015; 51(16):3371-4. DOI: 10.1039/c4cc07688e. View

Li C, Wang Z, Wang L, Zhang C . Biosensors for epigenetic biomarkers detection: A review. Biosens Bioelectron. 2019; 144:111695. DOI: 10.1016/j.bios.2019.111695. View

Luo H, Wei W, Ye Z, Zheng J, Xu R . Liquid Biopsy of Methylation Biomarkers in Cell-Free DNA. Trends Mol Med. 2021; 27(5):482-500. DOI: 10.1016/j.molmed.2020.12.011. View

Ushijima H, Maekawa R, Igarashi E, Akashi S . Rapid and Definitive Analysis of In Vitro DNA Methylation by Nano-electrospray Ionization Mass Spectrometry. J Am Soc Mass Spectrom. 2019; 30(11):2335-2346. PMC: 6828984. DOI: 10.1007/s13361-019-02304-5. View

10.

Moisoiu V, Stefancu A, Iancu S, Moisoiu T, Loga L, Dican L . SERS assessment of the cancer-specific methylation pattern of genomic DNA: towards the detection of acute myeloid leukemia in patients undergoing hematopoietic stem cell transplantation. Anal Bioanal Chem. 2019; 411(29):7907-7913. DOI: 10.1007/s00216-019-02213-2. View

11.

Hambalek J, Kong J, Brown C, Munoz H, Horn T, Bogumil M . Methylation-Sensitive Loop-Mediated Isothermal Amplification (LAMP): Nucleic Acid Methylation Detection through LAMP with Mobile Fluorescence Readout. ACS Sens. 2021; 6(9):3242-3252. DOI: 10.1021/acssensors.1c00902. View

12.

Kerachian M, Javadmanesh A, Azghandi M, Mojtabanezhad Shariatpanahi A, Yassi M, Shams Davodly E . Crosstalk between DNA methylation and gene expression in colorectal cancer, a potential plasma biomarker for tracing this tumor. Sci Rep. 2020; 10(1):2813. PMC: 7028731. DOI: 10.1038/s41598-020-59690-0. View

13.

Matulakul P, Vongpramate D, Kulchat S, Chompoosor A, Thanan R, Sithithaworn P . Development of Low-Cost AuNP-Based Aptasensors with Truncated Aptamer for Highly Sensitive Detection of 8-Oxo-dG in Urine. ACS Omega. 2020; 5(28):17423-17430. PMC: 7377066. DOI: 10.1021/acsomega.0c01834. View

14.

Jiang H, Ou Z, He Y, Yu M, Wu S, Li G . DNA methylation markers in the diagnosis and prognosis of common leukemias. Signal Transduct Target Ther. 2020; 5(1):3. PMC: 6959291. DOI: 10.1038/s41392-019-0090-5. View

15.

Straussman R, Nejman D, Roberts D, Steinfeld I, Blum B, Benvenisty N . Developmental programming of CpG island methylation profiles in the human genome. Nat Struct Mol Biol. 2009; 16(5):564-71. DOI: 10.1038/nsmb.1594. View

16.

Dadmehr M, Hosseini M, Hosseinkhani S, Ganjali M, Khoobi M, Behzadi H . DNA methylation detection by a novel fluorimetric nanobiosensor for early cancer diagnosis. Biosens Bioelectron. 2014; 60:35-44. DOI: 10.1016/j.bios.2014.03.033. View

17.

Liang W, Zhao Y, Huang W, Gao Y, Xu W, Tao J . Non-invasive diagnosis of early-stage lung cancer using high-throughput targeted DNA methylation sequencing of circulating tumor DNA (ctDNA). Theranostics. 2019; 9(7):2056-2070. PMC: 6485294. DOI: 10.7150/thno.28119. View

18.

Daugaard I, Dominguez D, Kjeldsen T, Kristensen L, Hager H, Wojdacz T . Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma. Sci Rep. 2016; 6:35807. PMC: 5080630. DOI: 10.1038/srep35807. View

19.

Feng Q, Wang M, Qin L, Wang P . Dual-Signal Readout of DNA Methylation Status Based on the Assembly of a Supersandwich Electrochemical Biosensor without Enzymatic Reaction. ACS Sens. 2019; 4(10):2615-2622. DOI: 10.1021/acssensors.9b00720. View

20.

Li Z, Pi T, Yan X, Tang X, Deng R, Zheng X . Label-free and enzyme-free one-step rapid colorimetric detection of DNA methylation based on unmodified gold nanoparticles. Spectrochim Acta A Mol Biomol Spectrosc. 2020; 238:118375. DOI: 10.1016/j.saa.2020.118375. View