Nanoribbon Biosensor in the Detection of miRNAs Associated with Colorectal Cancer

A nanoribbon biosensor (NRBS) was developed to register synthetic DNAs that simulate and are analogous to miRNA-17-3p associated with colorectal cancer. Using this nanoribbon biosensor, the ability to detect miRNA-17-3p in the blood plasma of a patient diagnosed with colorectal cancer has been demonstrated. The sensing element of the NRBS was a nanochip based on a silicon-on-insulator (SOI) nanostructure. The nanochip included an array of 10 nanoribbons and was designed with the implementation of top-down technology. For biospecific recognition of miRNA-17-3p, the nanochip was modified with DNA probes specific for miRNA-17-3p. The performance of the nanochip was preliminarily tested on model DNA oligonucleotides, which are synthetic analogues of miRNA-17-3p, and a detection limit of ~10−17 M was achieved. The results of this work can be used in the development of serological diagnostic systems for early detection of colorectal cancer.

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Early detection of colorectal cancer: A proteomic screening study for plasma biomarkers.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.415 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 415-415

Author(s):

Stine Buch Thorsen ◽

Martin Lundberg ◽

Erika Assarsson ◽

Nick Gee ◽

Mick Knowles ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Cross Reactivity ◽

Plasma Samples ◽

Regional Lymph Nodes ◽

Cancer Disease ◽

Dna Oligonucleotides ◽

Early Markers ◽

Screening Study ◽

Specific Proteins

415 Background: Colorectal cancer (CRC) is the third most frequent cancer disease in the US. As the 5 year survival is closely associated to stage of disease at the time of diagnosis, patients with localized tumor limited to the colon or rectum have more than 90% chance of 5 year survival, while tumors spreading to regional lymph nodes or to distant organs, have a 5 year survival rate of 69% and 12%, respectively. Since late diagnosis is equal to a poor prognosis for the patients, biomarker guided early detection could make a difference for these patients. One strategy is blood based assays, where we hypothesis that a tumor and its microenvironment will lead to a deposition of specific proteins in the blood. However, due to the complexity of plasma, it is not only a biological but also a technical challenge to detect the proteins specific for CRC. Consequently, we combined the technical evaluation of multiplex proximity probing assays (PPA) with the search for relevant biomarkers for CRC. Each of the protein assays were based on thorough literature studies on the biology of CRC. Methods: Proteins were measured using multiplex PPA. Each assay was constructed from commercially available antibodies conjugated to two DNA oligonucleotides. When the antibodies from one assay bind the target protein simultaneously, it enables the DNA oligonucleotides to be either enzymatic ligated or extended to a PCR amplicon. This PCR amplicon reflects the identity of the proteins and can be quantified by real-time PCR. We evaluated the assays and searched for potential early markers using a collection of case-control plasma samples from a larger endoscopy study. In total we measure the levels of 150 different proteins in 296 human plasma samples from 74 CRC patients, 74 healthy individuals, 74 adenoma patients, and 74 patients with non-cancer diseases. Results: We have a successrate of 80%, the sensitivity is for most assays below 5 pM, and we find no cross-reactivity in chicken plasma for any of the assays. We previous reported that CEA, TIMP-1, CA242, and IL8 were upregulated in CRC plasma. These proteins were also identified in our extended study and the data will be presented. Conclusions: We find potential early markers, which we will validate in new sample material.

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Detection of Marker miRNAs, Associated with Prostate Cancer, in Plasma Using SOI-NW Biosensor in Direct and Inversion Modes

Sensors ◽

10.3390/s19235248 ◽

2019 ◽

Vol 19 (23) ◽

pp. 5248 ◽

Cited By ~ 2

Author(s):

Yuri Ivanov ◽

Tatyana Pleshakova ◽

Kristina Malsagova ◽

Leonid Kurbatov ◽

Vladimir Popov ◽

...

Keyword(s):

Prostate Cancer ◽

High Sensitivity ◽

Storage Conditions ◽

Silicon On Insulator ◽

Diagnostic Systems ◽

Buffer Solution ◽

Dna Oligonucleotides ◽

Long Term Storage ◽

Target Nucleic Acid ◽

Biosensor Chip

Information about the characteristics of measuring chips according to their storage conditions is of great importance for clinical diagnosis. In our present work, we have studied the capability of chips to detect nanowire biosensors when they are either freshly prepared or have been stored for either one or two years in a clean room. Potential to detect DNA oligonucleotides (oDNAs)—synthetic analogues of microRNAs (miRNAs) 198 and 429 that are associated with the development of prostate cancer (PCa)—in buffer solution was demonstrated using a nanowire biosensor based on silicon-on-insulator structures (SOI-NW biosensor). To provide biospecific detection, nanowire surfaces were sensitized with oligonucleotide probes (oDNA probes) complimentary to the known sequences of miRNA 183 and 484. In this study it is demonstrated that freshly prepared SOI-NW biosensor chips with n-type conductance and immobilized oDNA probes exhibit responses to the addition of complimentary oDNAs in buffer, leading to decreases in chips’ conductance at a concentration of 3.3 × 10−16 M. The influence of storage time on the characteristics of SOI-NW biosensor chips is also studied herein. It is shown that a two-year storage of the chips leads to significant changes in their characteristics, resulting in “inverse” sensitivity toward negatively charged oDNA probes (i.e., through an increase in chips’ conductance). It is concluded that the surface layer makes the main contribution to conductance of the biosensor chip. Our results indicate that the detection of target nucleic acid molecules can be carried out with high sensitivity using sensor chips after long-term storage, but that changes in their surface properties, which lead to inversed detection signals, must be taken into account. Examples of the applications of such chips for the detection of cancer-associated microRNAs in plasma samples of patients with diagnosed prostate cancer are given. The results obtained herein are useful for the development of highly sensitive nanowire-based diagnostic systems for the revelation of (prostate) cancer-associated microRNAs in human plasma.

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Early detection of colorectal cancer from patient blood plasma using microRNA-based q-rt-PCR

10.1158/diag-10-b2 ◽

2010 ◽

Author(s):

Søren J. Nielsen ◽

Nana Jacobsen ◽

Jacob U. Fog ◽

Hanni Willenbrock ◽

Adam Baker ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Blood Plasma ◽

Rt Pcr

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Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer: A Guide for Patients, Their Families and Friends

PsycEXTRA Dataset ◽

10.1037/e506032012-001 ◽

2000 ◽

Cited By ~ 1

Author(s):

◽

Keyword(s):

Colorectal Cancer ◽

Early Detection

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Detector-C: A Blood-based IVD with High Sensitivity and Specificity for Early Detection and Screening of Colorectal Cancer

Zeitschrift für Gastroenterologie ◽

10.1055/s-0030-1263628 ◽

2010 ◽

Vol 48 (08) ◽

Author(s):

A Rosenthal ◽

H Köppen ◽

R Musikowski ◽

R Schwanitz ◽

J Behrendt ◽

...

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Sensitivity And Specificity ◽

High Sensitivity

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Biomarkers for Early Detection of Colitis-associated Colorectal Cancer - Current Concepts, Future Trends

Current Drug Targets ◽

10.2174/1389450121666200220123844 ◽

2020 ◽

Vol 22 (1) ◽

pp. 137-145

Author(s):

Tomasz Mackiewicz ◽

Aleksander Sowa ◽

Jakub Fichna

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Cancer Development ◽

Sporadic Colorectal Cancer ◽

Future Trends ◽

Significant Progress ◽

Current Standard ◽

Risk Of Cancer ◽

Histological Testing ◽

Made In

: Colitis-associated colorectal cancer (CAC) remains a critical complication of ulcerative colitis (UC) with mortality of approximately 15%, which makes early CAC diagnosis crucial. The current standard of surveillance, with repetitive colonoscopies and histological testing of biopsied mucosa samples is burdensome and expensive, and therefore less invasive methods and reliable biomarkers are needed. Significant progress has been made thanks to continuous extensive research in this field, however no clinically relevant biomarker has been established so far. This review of the current literature presents the genetic and molecular differences between CAC and sporadic colorectal cancer and covers progress made in the early detection of CAC carcinogenesis. It focuses on biomarkers under development, which can be easily tested in samples of body fluids or breath and, once made clinically available, will help to differentiate between progressors (UC patients who will develop dysplasia) from non-progressors and enable early intervention to decrease the risk of cancer development.

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Early Detection of Colorectal Cancer and Population Screening Tests

Colorectal Cancer - From Prevention to Patient Care ◽

10.5772/27404 ◽

2012 ◽

Author(s):

Christos Lionis ◽

Elena Petelos

Keyword(s):

Colorectal Cancer ◽

Early Detection ◽

Population Screening ◽

Screening Tests

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Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

BMC Gastroenterology ◽

10.1186/s12876-021-01759-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Chang Woo Kim ◽

Hyunjin Kim ◽

Hyoung Rae Kim ◽

Bong-Hyeon Kye ◽

Hyung Jin Kim ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Early Detection ◽

Prospective Trial ◽

Screening Colonoscopy ◽

Quantitative Detection ◽

Screening Programs ◽

Crc Screening ◽

Stool Dna ◽

Dna 2

Abstract Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1.

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