Biomarkers For Detection Of Cancer Research Articles

Surface protein analysis of breast cancer exosomes using visualized strategy on centrifugal disk chip

Breast cancer, the most common cancer among women worldwide, lacks specific tumor markers for accurate diagnosis. Recent advances have highlighted tumor-derived exosomes as a promising non-invasive biomarker for cancer detection. Continuous monitoring of surface protein markers on exosomes in the blood could offer valuable insights for breast cancer diagnosis. However, integrating the isolation and detection of exosomes from whole blood is bulky, time-consuming, and requires professional operations. To address this difficulty, we developed a method of integrated centrifugal disk chip (CD chip) exosome enrichment directly from whole blood followed by a colorimetric visualization strategy for multiplex analysis. The disc consists of multi-chambers and multi-microchannels with immediate smartphone-enabled processing of colorimetric results. The combination of CEA + CA125 + EGFR on-chip detection could significantly differentiate the different stages of cancer in tumor-bearing mice and successfully distinguish between breast cancer patients and healthy individuals. Crucially, small volumes (100 μL) of blood samples were adequate. In addition, the chip was simple and fast, with results within 10 min, which provides immediate exosomal information through consecutive blood sampling, which could potentially result in a more timely and well-informed clinical breast cancer diagnosis.

A 96-Well LED Array for Multiplexed Photoelectrochemical Detection of Nucleic Acids.

Photoelectrochemical detection of nucleic acid-based cancer biomarkers offers opportunities for highly sensitive, selective, and fast quantitative detection using low-cost measurement instruments. In order to establish itself as a standard method for identifying and quantifying nucleic acids, we have developed a multiplexing strategy using LED technology for photoelectrochemical detection in 96 samples simultaneously. A dedicated setup based on the 96-well plate configuration with a custom-made 96-well LED array was developed. Subsequently, a proof-of-concept study was performed for three miRNAs that are associated with prostate cancer, i.e., miRNA-141, miRNA-145, and miRNA-375. First, measurements with photosensitizer chlorin e6 and redox reporter hydroquinone free in solution proved the proper functioning of the multiplexed detection. Second, the photoelectrochemical detection of the three miRNAs at 24 nM levels was successfully demonstrated. Thereafter, linear calibration curves (R2 > 0.9 for all analytes) were made with plasma spiked with 8-500 pM miRNA. This work presents the first system for multiplexed high-throughput photoelectrochemical detection, allowing it potentially to become a cost-effective and faster alternative to RT-qPCR and gene sequencing techniques in the future.

Design and optimization of refractive index biosensor for MDA-MB-231 and MCF-7 breast cancer biomarker detection

Breast cancer is the leading malignancy in women and the 2nd widespread cancer globally. Earlier identification of breast cancer can improve treatment outcomes and prevent metastasis beyond the breast. Traditional screening tests are not sensitive enough for early diagnosis and have extended detection periods. Recent studies have explored diversified Breast cancer biosensor techniques, including optical, electrical, electrochemical, and mechanical biosensors. This paper nominates a circlet with a large plus sign refraction indices biosensor for the evaluation of two distinct breast cancer cells namely, MDA-MB-231 and MCF-7. The supreme sensitivity has been viewed as 1714.28 nm/RIU for the MDA-MB-231 and 1714.28 nm/RIU for the MCF-7. The supreme quality factor (QF) value for UC1(usual cell of MDA-MB-231) is 10.52, for CC1(cancer cell of MDA-MB-231) is 11.94, for UC2 (usual cell of MCF-7) is 10.64, and for CC2 (cancer cell of MCF-7) is 12.09. The minimal detection value (DL) for UC1 is 0.1573, CC1 is 0.1360, UC2 is 0.1554, and CC2 is 0.1341. This nominated sensor has the potential to sense breast tumor biomarkers.

Development of a simple HPLC method for the determination of urinary O-aminohippuric acid (OAH) and an establishment of OAH reference interval

Background: O-aminohippuric acid (OAH) is considered a low-abundance urinary fluorescent metabolite with the potential to be an innovative lung cancer biomarker. There is a lack of simple methods for measuring urinary OAH metabolite, and the measurement needs to be normalized by urinary creatinine, which is produced at a constant rate. Thus, the newly developed method must be able to determine urinary creatinine and OAH simultaneously in the same run. Objective: This work aimed to develop and validate a simple high-performance liquid chromatography (HPLC) method for measuring urinary OAH and to establish the reference intervals of OAH in healthy individuals. Materials and methods: We synthesized OAH standard in a simple route and optimized simple HPLC method for simultaneous measurement of creatinine and OAH in a single run. Analysis was performed on a RP-C18 column with a gradient elution system of acetonitrile - ammonium acetate buffer (pH 6.5, 100 mM). After implementing optimal conditions, the procedure was compiled according to the International Council for Harmonisation (ICH) validation parameters. The developed method was used for the establishment of reference intervals of a total of 120 random urine samples of healthy individuals. Results: The linear range of the calibration curve for creatinine and OAH were 1-1000 µg/mL and 0.1-100 µg/mL, respectively. The recoveries ranged for both metabolites were between 91.35 % and 109.12%. The relative standard deviations (RSDs) for the intra-day and inter-day results ranged from 0.11-0.66 % to 0.16-1.73 %, respectively. The limits of detection (LOD) and quantification (LOQ) were 0.258 µg/mL and 0.783 µg/mL for creatinine, while OAH was 0.045 µg/mL and 0.137 µg/mL, respectively. The method was successfully applied to establish reference intervals of OAH in healthy individuals and was defined as 0.420-2.287 mmol/mol creatinine. Conclusion: According to various validated parameters, the proposed method was proven to quantify urinary OAH and creatinine in a single run. It can also be analyzed noninvasively without additional sample processing. Reported herein is the first establishment of OAH reference intervals in healthy individuals, which may benefit the utilization of OAH as a noninvasive biomarker for lung cancer detection in the future.

Optimization of Nanowell-Based Label-Free Impedance Biosensor Based on Different Nanowell Structures.

Nanowell-based impedance-based label-free biosensors have demonstrated significant advantages in sensitivity, simplicity, and accuracy for detecting cancer biomarkers and macromolecules compared to conventional impedance-based biosensors. Although nanowell arrays have previously been employed for biomarker detection, a notable limitation exists in the photolithography step of their fabrication process, leading to a reduced efficiency rate. Historically, the diameter of these nanowells has been 2 μm. To address this issue, we propose alternative geometries for nanowells that feature larger surface areas while maintaining a similar circumference, thereby enhancing the fabrication efficiency of the biosensors. We investigated three geometries: tube, spiral, and quatrefoil. Impedance measurements of the samples were conducted at 10 min intervals using a lock-in amplifier. The study utilized interleukin-6 (IL-6) antibodies and antigens/proteins at a concentration of 100 nM as the target macromolecules. The results indicated that tube-shaped nanowells exhibited the highest sensitivity for detecting IL-6 protein, with an impedance change of 9.55%. In contrast, the spiral, quatrefoil, and circle geometries showed impedance changes of 0.91%, 0.95%, and 1.62%, respectively. Therefore, the tube-shaped nanowell structure presents a promising alternative to conventional nanowell arrays for future studies, potentially enhancing the efficiency and sensitivity of biosensor fabrication.

A label-free and signal-amplifiable fluorescent biosensor based on aptamer-conjugated gold nanoparticles and hybridization chain reaction for determination of carcinoembryonic antigen.

The sensitive detection of cancer biomarkers is crucial for early accurate diagnostics and therapy of cancer patients. Carcinoembryonic antigen (CEA) is a tumor-associated antigen derived from colon cancer and embryonic tissues. In this study, we have developed a label-free fluorescence biosensing platform for the quantification of CEA with the "turn-on" signal output. This platform employs a label-free strategy that incorporates an aptamer-modified gold nanoparticle (Apt@AuNP) probe for the recognition of CEA, in combination with hybridization chain reaction (HCR) amplification. In the presence of target CEA, Apt@AuNPs selectively capture CEA, resulting in a reduction of subsequent complementary chains (CP) binding on Apt@AuNPs. The remaining CP, acting as the initiator sequence for HCR, triggers the HCR, leading to the formation of abundant G-quadruplex structures. By employing Thioflavin T (ThT) for the formation of G-quadruplex/ThT complexes, the biosensor exhibits a significant enhancement of the fluorescence signal. Under optimized conditions, the biosensor platform demonstrates a limit of detection of 0.03 nM and a linear range from 0.1 to 2.5nM. Additionally, the specificity investigation reveals the high selectivity of this fluorescent biosensor. Finally, the performance of this method has been validated by successfully detecting CEA in real-life samples, highlighting its potential for clinical applications.

Unlocking the potential of exosomes: A new frontier in liver cancer liquid biopsy

Liquid biopsy has emerged as one of the non-invasive diagnostic strategies for cancer, offering significant advantages over traditional tissue biopsies. Exosomes the nanoscale extracellular vesicles, have significantly been in the spotlight of research and investigation as highly informative biomarkers in liquid biopsy. These vesicles, which are secreted by a variety of cells, including tumor cells, contain useful information on the molecular characteristics of the parent cell and could be used as a mirror into the processes underlying cancer biology. The analysis of the biomolecular exosomal cargo, including proteins, nucleic acids, and lipids, has shown great promise for the development of sensitive and specific liquid biopsy-based biomarkers for cancer detection, monitoring, and prognosis. This review discusses the role of exosomes in the liver cancer development and metastatic process, including their ability to transfer oncogenic material and facilitate tumor progression. It also explores the application of exosomes as a tool for early cancer detection, monitoring disease status, and predicting prognosis, with a specific focus on liver cancer. Exosomes hold great promise as a minimally invasive liquid biopsy approach that could revolutionize the way we diagnose and manage this deadly disease.

Proteomic Profiling of Serum of Women with Bi-Rads 1 to 5: Identification of Potential Complementary Biomarkers for Early Detection of Breast Cancer

Proteomic Profiling of Serum of Women with Bi-Rads 1 to 5: Identification of Potential Complementary Biomarkers for Early Detection of Breast Cancer

Screen-Printed Electrodes as Low-Cost Sensors for Breast Cancer Biomarker Detection.

This review explores the emerging role of screen-printed electrodes (SPEs) in the detection of breast cancer biomarkers. We discuss the fundamental principles and fabrication techniques of SPEs, highlighting their adaptability and cost-effectiveness. The review examines various modification strategies, including nanomaterial incorporation, polymer coatings, and biomolecule immobilization, which enhance sensor performance. We analyze the application of SPEs in detecting protein, genetic, and metabolite biomarkers associated with breast cancer, presenting recent advancements and innovative approaches. The integration of SPEs with microfluidic systems and their potential in wearable devices for continuous monitoring are explored. While emphasizing the promising aspects of SPE-based biosensors, we also address current challenges in sensitivity, specificity, and real-world applicability. The review concludes by discussing future perspectives, including the potential for early screening and therapy monitoring, and the steps required for clinical implementation. This comprehensive overview aims to stimulate further research and development in SPE-based biosensors for improved breast cancer management.

Protein Biomarkers of Gastric Preneoplasia and Cancer Lesions in Blood: A Comprehensive Review.

Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. It is often associated with a bad prognosis because of its asymptomatic phenotype until advanced stages, highlighting the need for its prevention and early detection. GC development is preceded by the emergence of gastric preneoplasia lesions (GPNLs), namely atrophic gastritis (AG), intestinal metaplasia (IM), and dysplasia (DYS). GC is currently diagnosed by endoscopy, which is invasive and costly and has limited effectiveness for the detection of GPNLs. Therefore, the discovery of non-invasive biomarkers in liquid biopsies, such as blood samples, in order to identify the presence of gastric preneoplasia and/or cancer lesions at asymptomatic stages is of paramount interest. This comprehensive review provides an overview of recently identified plasma/serum proteins and their diagnostic performance for the prediction of GPNLs and early cancer lesions. Autoantibodies appear to be promising biomarkers for AG, IM and early gastric cancer detection, along with inflammation and immunity-related proteins and antibodies against H. pylori virulence factors. There is a lack of specific protein biomarkers with which to detect DYS. Despite the need for further investigation and validation, some emerging candidates could pave the way for the development of reliable, non-invasive diagnostic tests for the detection and prevention of GC.

Early detection of pancreatic cancer by comprehensive serum miRNA sequencing with automated machine learning.

Pancreatic cancer is often diagnosed at advanced stages, and early-stage diagnosis of pancreatic cancer is difficult because of nonspecific symptoms and lack of available biomarkers. We performed comprehensive serum miRNA sequencing of 212 pancreatic cancer patient samples from 14 hospitals and 213 non-cancerous healthy control samples. We randomly classified the pancreatic cancer and control samples into two cohorts: a training cohort (N = 185) and a validation cohort (N = 240). We created ensemble models that combined automated machine learning with 100 highly expressed miRNAs and their combination with CA19-9 and validated the performance of the models in the independent validation cohort. The diagnostic model with the combination of the 100 highly expressed miRNAs and CA19-9 could discriminate pancreatic cancer from non-cancer healthy control with high accuracy (area under the curve (AUC), 0.99; sensitivity, 90%; specificity, 98%). We validated high diagnostic accuracy in an independent asymptomatic early-stage (stage 0-I) pancreatic cancer cohort (AUC:0.97; sensitivity, 67%; specificity, 98%). We demonstrate that the 100 highly expressed miRNAs and their combination with CA19-9 could be biomarkers for the specific and early detection of pancreatic cancer.

Highly sensitive PEC immunosensor for CA15–3 detection based on Bi2S3-sensitized hexagonal ZnTiO3 and Au-functionalized ZnS

The biomarker CA15–3 plays a significant role in cancer diagnosis and therapeutic monitoring. In this study, a photoelectrochemical (PEC) immunosensor was designed using hexagonal ZnTiO3/Bi2S3 heterojunction as the photoactive material, and ZnS@Au as a label for the detection antibody to amplify the signal. The hexagonal ZnTiO3 serves as the substrate material, providing a stable photocurrent response, while Bi2S3 forms a band-matching heterostructure with ZnTiO3, facilitating the transfer of photogenerated electrons. Additionally, the narrow bandgap of Bi2S3 sensitizes the material, broadening its visible light response and further enhancing the photocurrent output. Moreover, square-shaped ZnS functionalized with Au NPs is employed as a quenching signal label, which effectively competed the photogenerated electrons and consumed electron donors in the electrolyte, thereby increasing the detection sensitivity. This sensor offers a broad detection range for CA15–3, from 0.001 U·mL−1 to 1000 U·mL−1, with a detection limit of 0.0003 U·mL−1, illustrating its potential for precise and reliable cancer biomarker detection.

Detecting cancer biomarkers using electrochemical composite nanomaterials tools

AbstractAnnually, cancer accounts for a large number of mortalities worldwide, underscoring the imperative for early‐stage detection as a public health priority. This article not only offers an in‐depth analysis of the synthesis, fabrication, design, and structural attributes of these nanomaterials but also provides a critical evaluation of their application in various electrochemical biosensing modalities, including amperometry, impedimetric, photoelectrochemical, potentiometric, and field‐effect transistor‐based sensors. A primary focus is placed on the importance of nanomaterials‐based biosensors in detecting cancer biomarkers, emphasizing their role in achieving enhanced sensitivity and specificity for detecting circulating tumor cells, nucleic acids, proteins, and exosomes, which are crucial indicators of malignancy. The article offers valuable insights into the detection of these biomarkers. It details their significance and relevance in the early diagnosis of various cancer types with nanomaterial‐enhanced electrochemical biosensors’ stability, reusability, and conductivity, shedding light on their practical applicability in real‐world scenarios. The manuscript concludes by addressing existing challenges and outlining prospective avenues for future research, emphasizing the need for continued innovation and exploration in this burgeoning field.

CRISPR-Cas target recognition for sensing viral and cancer biomarkers.

Nucleic acid-based diagnostics is a promising venue for detection of pathogens causing infectious diseases and mutations related to cancer. However, this type of diagnostics still faces certain challenges, and there is a need for more robust, simpleand cost-effective methods. Clustered regularly interspaced short palindromic repeats (CRISPRs), the adaptive immune systems present in the prokaryotes, has recently been developed for specific detection of nucleic acids. In this review, structural and functional differences of CRISPR-Cas proteins Cas9, Cas12and Cas13 are outlined. Thereafter, recent reports about applications of these Cas proteins for detection of viral genomes and cancer biomarkers are discussed. Further, we highlight the challenges associated with using these technologies to replace the current diagnostic approaches and outline the points that need to be considered for designing an ideal Cas-based detection system for nucleic acids.

Confinement Effect Enhanced Bipolar Electrochemistry: Structural Color Coding Coupled with Wireless Electrochemiluminescence Imaging Technology.

In this work, SiO2/CNTs photonic crystal beads were constructed by doping CNTs into SiO2 photonic crystals, which have an angle-independent responsive structural color and can be used as bipolar electrodes due to their good electrical conductivity. In addition, the bipolar electrode-electrochemiluminescence (BPE-ECL) experiments and finite element simulation prove that the low driving voltage can trigger the bipolar electrode electrochemical reactions by confinement effect. Inspired by this, it is the first to combine the SiO2/CNTs structural color coding scheme with low-drive voltage induced wireless BPE-ECL imaging based on the confinement effect of microchannels to achieve simultaneous immune detection of ovarian cancer biomarkers (CA125, CEA, AFP). The detection limits of successfully constructed high-throughput BPE-ECL biosensor for AFP, CEA, and CA125 are 0.72 ng/mL, 0.95 ng/mL, and 1.03 U/mL, respectively, and have good stability and specificity, which expands the application of electrochemiluminescence and lays a foundation for the development of electrochemiluminescence coding technology.

An super sensitive Multi-Modal controlled release biosensor with label- and enzyme- free assisted single step simultaneously detect multiple breast cancer biomarkers

Despite the fact that homogeneous biosensing strategies have been proven to be advantageous, it remains a difficult task to identify multiple tumor biomarkers. Our proposition entails the creation of a groundbreaking biosensor that combines electrochemical and fluorescent techniques, enabling simultaneous detect multiple biomarkers with label- and enzyme-free assistance in a single step. Porous UIO-66-NH2 nanovessels loaded with 3,3′,5,5′ −tetramethylbenzidine (TMB) and methylene blue (MB) double signal dyes, along with double-stranded DNA (dsDNA) formed by the aptamer chain of human epidermal growth factor receptor-2 (HER2) and estrogen receptor (ER) and its complementary chain as a gated switch to the envelope MOFs, were utilized to create functional MOFs (dsDNA@MB@UIO and dsDNA@TMB@UIO). When HER2 and ER targets are present, the chain replacement reaction led to the formation of a biomarker-aptamer complex, resulting in the destruction of the dsDNA structure on the surface of MOF and the liberation of MB and TMB. The concentration of the two target biomarkers determines the strength of the electrochemical and fluorescent signals produced. By combining targeted biomarkers, signal enhancement, and dual-signal detection into one unified process, the amount of test error caused by the multi-step detection needed in prior studies is significantly decreased. We executed the detect HER2 and ER, achieving detection limits of 4.7 and 5.9 fg/mL in 4.7–1000 pg/mL linear range with good selectivity, stability, reproducibility, and acceptable applicability. The proposed biosensor for developing dsDNA@MB@UIO and dsDNA@TMB@UIO is promising for the early and sensitive detection of cancer biomarkers.

Circulating miR-30b-5p Level in Plasma as a Potential Biomarker for Early Detection of Breast Cancer

Circulating miR-30b-5p Level in Plasma as a Potential Biomarker for Early Detection of Breast Cancer

Disposable Zirconium trisulfide-Reduced graphene oxide modified conducting thread based electrochemical biosensor for lung cancer diagnosis

Flexible technology in sensors have received much attention in monitoring of human health through various physiological indicators. Thus, it drawn a lot of interest in the development of flexible substrate for the diagnosis of various diseases via analysis of analytes. Present work focusses on the development of ecofriendly, portable, flexible, conducting thread (Th) and used as smart substrate for fabrication of biosensor towards ultrasensitive detection of the lung cancer biomarker (cytoskeleton-associated protein 4; CKAP4). The zirconium trisulfide-reduced graphene oxide nanocomposite and poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) modified cotton thread based biosensor was fabricated via dip coating method. Next, successive immobilization of monoclonal antibodies of CKAP4 (anti-CKAP4) and bovine serum albumin (BSA) was performed via drop cast approach using fabricated electrode [nZrS3@rGO/PEDOT:PSS/Th]. The response of fabricated electrode (BSA/anti-CKAP4/ZrS3@rGO/PEDOT:PSS/Th) was recorded electrochemically versus CKAP4 concentration via chronoamperometry (CA). The results showed wider linear detection range of 6.25-800 pg mL−1, excellent sensitivity of 85.2 µA[log(pg mL−1)]-1cm−2 with good stability up to 42 days. The response of fabricated biosensor was supported by investigating response of CKAP4 biomarker present in patients of lung cancer (concentration as determined through enzyme-linked immunosorbent assay) and obtained results exhibited excellent correlation with that of standard samples.

Sensors Based on Molecularly Imprinted Polymers in the Field of Cancer Biomarker Detection: A Review.

Biomarkers play a pivotal role in the screening, diagnosis, prevention, and post-treatment follow-up of various malignant tumors. In certain instances, identifying these markers necessitates prior treatment due to the complex nature of the tumor microenvironment. Consequently, advancing techniques that exhibit selectivity, specificity, and enable streamlined analysis hold significant importance. Molecularly imprinted polymers (MIPs) are considered synthetic antibodies because they possess the property of molecular recognition with high selectivity and sensitivity. In recent years, there has been a notable surge in the investigation of these materials, primarily driven by their remarkable adaptability in terms of tailoring them for specific target molecules and integrating them into diverse analytical technologies. This review presents a comprehensive analysis of molecular imprinting techniques, highlighting their application in developing sensors and analytical methods for cancer detection, diagnosis, and monitoring. Therefore, MIPs offer great potential in oncology and show promise for improving the accuracy of cancer screening and diagnosis procedures.

CircCNNs, a convolutional neural network framework to better understand the biogenesis of exonic circRNAs

Circular RNAs (circRNAs) as biomarkers for cancer detection have been extensively explored, however, the biogenesis mechanism is still elusive. In contrast to linear splicing (LS) involved in linear transcript formation, the so-called back splicing (BS) process has been proposed to explain circRNA formation. To investigate the potential mechanism of BS via the machine learning approach, we curated a high-quality BS and LS exon pairs dataset with evidence-based stringent filtering. Two convolutional neural networks (CNN) base models with different structures for processing splicing junction sequences including motif extraction were created and compared after extensive hyperparameter tuning. In contrast to the previous study, we are able to identify motifs corresponding to well-established BS-associated genes such as MBNL1, QKI, and ESPR2. Importantly, despite prevalent high false positive rates in existing circRNA detection pipelines and databases, our base models demonstrated a notable high specificity (greater than 90%). To further improve the model performance, a novo fast numerical method was proposed and implemented to calculate the reverse complementary matches (RCMs) crossing two flanking regions and within each flanking region of exon pairs. Our CircCNNs framework that incorporated RCM information into the optimal base models further reduced the false positive rates leading to 88% prediction accuracy.