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Ultrasensitive detection of cancer biomarker microRNA by amplification of fluorescence of lanthanide nanoprobes

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Nano Research 2018年第1期11卷 264-273页

作者： Lianyu Lu Datao Tu Yan Liu Shanyong Zhou Wei Zheng Xueyuan Chen College of Chemistry Fuzhou University Fuzhou 350116 China CAS Key Laboratory of Design and Assembly of Functional Nanostructures and Fujian Provincial Key Laboratory of Nanomaterials Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences Fuzhou 350002 China

Sensitive detection of cancer biomarker microRNAs （miRNAs） is of vital importance for cancer diagnosis and treatment. Nonetheless, the detection sensitivity in the existing miRNA bioassays is severely limited by the structural characteristics of miRNA （including small length and high sequence homology） because most of these methods are based on target amplification. Herein, we report a novel approach to sensitive and specific detection of low-abundance miRNA via a unique strategy of nanoprobe dissolution-enhanced fluorescence amplification, in which a capture probe featuring molecular beacon structure is designed. By means of this strategy, miRNA-21 was detected in a linear range from 10 fM to 100 pM with a detection limit as low as 1.38 fM. High selectivity of the newly developed biosensor was demonstrated by the good discrimination against a target with a single-base mismatch. Furthermore, this assay was used for the detection of miRNA-21 added into fetal bovine serum samples with the recovery in the range of 90.2%--108% and coefficients of variation below 10.1%, indicating its promising applications to RNA immunoassays and early cancer diagnosis.

关键词： microRNA lanthanide nanoparticles fluorescence amplification cancer biomarker molecular beacon

A review on graphene-based materials as versatile cancer biomarker sensors

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Frontiers of Materials Science 2020年第4期14卷 353-372页

作者： Shalmali BASU Kamalika SEN Department of Chemistry University of Calcutta92 APC RoadKolkata 700009India

Early detection of cancer has multitude of advantages like early diagnosis,reduced risk,ease in the treatment and follow up of *** and developed techniques are always under research to control the spreading *** is an emerging star in biomedical field as it exhibits exceptional thermal,electrical and optical ***,we review application of graphene-based materials in developing biosensing devices for the detection of different cancer biomarkers at concentrations down to sub-toxic *** analytical methodologies chosen for sensing have been undertaken and their performance and background have been *** trend of use of these methodologies can also be perceived from the graphical data presented.

关键词： graphene cancer biomarker biosensing analytical methods

Towards precision medicine:advances in 5-hydroxymethylcytosine cancer biomarker discovery in liquid biopsy

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cancer Communications 2019年第1期39卷 113-121页

作者： Chang Zeng Emily Kunce Stroup Zhou Zhang Brian C-HChiu Wei Zhang Driskill Graduate Program in Life Sciences Northwestern University Feinberg School of MedicineChicagoIL 60611USA Department of Preventive Medicine Northwestern University Feinberg School of Medicine680 N.Lake Shore Dr.Suite 1400ChicagoIL 60611USA Department of Public Health Sciences University of ChicagoChicagoIL 60637USA The Robert H.Lurie Comprehensive cancer Center Northwestern University Feinberg School of MedicineChicagoIL 60611USA Institute of Precision Medicine Jining Medical UniversityJining 272067ShandongP.R.China.

Robust and clinically convenient biomarkers for cancer diagnosis,early detection,and prognosis have great potential to improve patient survival and are the key to precision *** advent of next-generation sequencing technologies enables a more sensitive and comprehensive profiling of genetic and epigenetic information in tumor-derived *** are now able to monitor the dynamics of tumorigenesis in new dimensions,such as using circulating cell-free DNA(cfDNA)and tumor DNA(ctDNA).Mutation-based assays in liquid biopsy cannot always provide consistent results across studies due partly to intra-and inter-tumoral heterogeneity as well as technical *** contrast,epigenetic analysis of patient-derived cfDNA is a promising alternative,especially for early detection and disease surveillance,because epigenetic modifications are tissue-specific and reflect the dynamic process of cancer ***,cfDNA-based epigenetic assays are emerging to be a highly sensitive,minimally invasive tool for cancer diagnosis and prognosis with great potential in future precise care of cancer *** major obstacle for applying epigenetic analysis of cfDNA,however,has been the lack of enabling techniques with high sensitivity and technical *** this review,we summarized the advances in epigenome-wide profiling of 5-hydroxymethyl-cytosine(5hmC)in cfDNA,focusing on the detection approaches and potential role as biomarkers in different cancer types.

关键词： Liquid biopsy Cell-free DNA Epigenetics cancer biomarker 5-Hydroxymethylcytosine

Development and optimization of an antibody array method for potential cancer biomarker detection

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The Journal of Biomedical Research 2011年第1期25卷 63-70页

作者： Shuangshuang Wang Ping Zhao Brian Cao Key Laboratory of Antibody Technology of Ministry of Health Nanjing Medical University Nanjing Jiangsu Province 210029 China Antibody Technology Laboratory Van Andel Research Institute Grand Rapids MI 49503 USA

biomarkers play an important role in the detection at an early stage of pancreatic cancer. The aim of the present study was to optimize the conditions of antibody arrays for detecting Hippocalcin-like 1 （HPCAL1）, phosphatidylethanolamine binding protein 1 （PEBP1）, lectin galactoside-binding soluble 7 （LGALS7）, and serpin peptidase inhibitor clade E member 2 （SERPINE2） as biomarkers for pancreatic cancer detection in a single assay and to investigate antibodies’ specificity and cross-reactivity. Capture antibodies against HPCAL1, PEBP1, LGALS7 and SERPINE2 were printed on nitrocellulose coated glass slides. HPCAL1, PEBP1, LGALS7 and SERPINE2 proteins with different concentrations were incubated with the capture antibodies at different temperatures for different time periods. Biotinylated detection antibodies recognizing a different epitope on the captured proteins and a secondary detection molecule （Streptavidin-PE） were used to detect fluorescent signals. The arrays showed the strongest signals when the concentration of the capture antibodies was at 500 μg/mL in PBST0.05 （PBS with 0.05% Tween-20）, and the slides were incubated overnight at 4°C. The lowest protein concentration for detection was 2 ng/mL. Each antibody demonstrated high specificity to the corresponding antigen in detecting a mixture of 4 proteins without significant cross-reactivity. The fluorescence and biomarker concentration displayed a linear correlation. The antibody microarray system could be a useful tool for potential biomarker detection for pancreatic cancer.

关键词： cancer biomarker HPCAL1 PEBP1 LGALS7 SERPINE2 antibody microarray

Proteomics techniques in protein biomarker discovery

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Quantitative Biology 2024年第1期12卷 53-69页

作者： Mahsa Babaei Soheila Kashanian Huang-Teck Lee Frances Harding Department of Biology Faculty of ScienceRazi UniversityKermanshahIran Faculty of Chemistry Sensor and Biosensor Research Center(SBRC)Razi UniversityKermanshahIran Nanobiotechnology Department Faculty of Innovative Science and TechnologyRazi UniversityKermanshahIran Centre for Marine Bioproducts Development Flinders UniversityAdelaideSouth AustraliaAustralia Monash Institute of Pharmaceutical Sciences Monash UniversityMelbourneNew South WalesAustralia

Protein biomarkers represent specific biological activities and processes, so they have had a critical role in cancer diagnosis and medical care for more than 50 years. With the recent improvement in proteomics technologies, thousands of protein biomarker candidates have been developed for diverse disease states. Studies have used different types of samples for proteomics diagnosis. Samples were pretreated with appropriate techniques to increase the selectivity and sensitivity of the downstream analysis and purified to remove the contaminants. The purified samples were analyzed by several principal proteomics techniques to identify the specific protein. In this study, recent improvements in protein biomarker discovery, verification, and validation are investigated. Furthermore, the advantages, and disadvantages of conventional techniques, are discussed. Studies have used mass spectroscopy (MS) as a critical technique in the identification and quantification of candidate biomarkers. Nevertheless, after protein biomarker discovery, verification and validation have been required to reduce the false-positive rate where there have been higher number of samples. Multiple reaction monitoring (MRM), parallel reaction monitoring (PRM), and selected reaction monitoring (SRM), in combination with stable isotope-labeled internal standards, have been examined as options for biomarker verification, and enzyme-linked immunosorbent assay (ELISA) for validation.

关键词： biomarker discovery cancer biomarker gel-based methods gel-free methods mass spectroscopy proteomics

Novel Graphene Biosensor Based on the Functionalization of Multifunctional Nano-bovine Serum Albumin for the Highly Sensitive Detection of cancer biomarkers

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Nano-Micro Letters 2019年第2期11卷 24-36页

作者： Lin Zhou Kun Wang Hao Sun Simin Zhao Xianfeng Chen Dahong Qian Hongju Mao Jianlong Zhao State Key Laboratory of Transducer Technology Key Laboratory of Terahertz Solid-State TechnologyShanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai 200050People’s Republic of China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240People’s Republic of China School of Electronic Engineering Bangor UniversityBangor LL57 1UTUK

A simple,convenient,and highly sensitive bio-interface for graphene field-effect transistors(GFETs) based on multifunctional nano-denatured bovine serum albumin(nano-dBSA) functionalization was developed to target cancer *** novel graphene–protein bioelectronic interface was constructed by heating to denature native BSA on the graphene substrate *** formed nano-d BSA film served as the cross-linker to immobilize monoclonal antibody against car-cinoembryonic antigen(anti-CEA mAb) on the graphene channel activated by EDC and *** nano-dBSA film worked as a self-protecting layer of graphene to prevent surface contamination by lithographic *** improved GFETbiosensor exhibited good specificity and high sensitivity toward the target at an ultralow concentration of 337.58 fg *** electrical detection of the binding of CEA followed the Hill model for ligand–receptor interaction,indicating the negative binding cooperativity between CEA and anti-CEA mAb with a dissociation constant of 6.82×*** multifunctional nano-dBSA functionalization can confer a new function to graphene-like 2D nanomaterials and provide a promising bio-functionalization method for clinical application in biosensing,nanomedicine,and drug delivery.

关键词： Bio-interface Multifunctional denatured BSA GFET biosensor cancer biomarker

cancer biomarkers discovery of methylation modification with direct high-throughput nanopore sequencing

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Cancer biomarkers discovery of methylation modification with...

Electrochemical Sensors Applied for In vitro Diagnosis

2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Junjie Zhang Shuilian Xie Shaogui Wan Gannan Medical University

cancer is a complex disease, driven by a combination of genetic and epigenetic alterations. DNA and RNA methylation modifications are the most common epigenetic events that play critical roles in cancer development and progression. Bisulfite converted sequencing is a widely used technique to detect base modifications in DNA methylation, but its main drawbacks lie in DNA degradation, lack of specificity,or short reads with low sequence diversity. The nanopore sequencing technology can directly detect base modifications in native DNA as well as RNA without harsh chemical treatment, compared to bisulfite sequencing. Furthermore, CRISPR/Cas9-targeted enrichment nanopore sequencing techniques are straightforward and cost-effective when targeting genomic regions are of interest. In this review, we mainly focus on DNA and RNA methylation modifications detection in cancer with the current nanopore sequencing approaches. We also present the respective strengths, weaknesses of nanopore sequencing techniques and their future translational applications in identification of epigenetic biomarkers for cancer detection and prognosis.

关键词： Nanopore sequencing cancer biomarker Cas9 enrichment DNA methylation RNA methylation

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Chemical Research in Chinese Universities 2021年第4期37卷 803-822页

作者： LI Duo WU Cha TANG Xuehui ZHANG Yue WANG Tie Life and Health Research Institute School of Chemistry and Chemical EngineeringTianjin University of TechnologyTianjin300384P.R.China Beijing National Laboratory for Molecular Sciences Key Laboratory of Analytical Chemistry for Living BiosystemsInstitute of ChemistryChinese Academy of SciencesBeijing100190P.R.China

Electrochemical sensing technology has received extensive attention from researchers for its unique detection and analysis methods as well as the promising applications in clinical *** with other detection methods,such as capillary electrophoresis,high‐performance liquid chromatography and liquid chromatography-tandem mass spectrometry,the electrochemical sensor overcomes the disadvantages of expensive cost and complicated operation,as an ideal device for in vitro *** this article,we mainly introduce some methods for the detection of biologically important compounds and cancer biomarkers,and briefly summarize the characteristics of these methods at *** then,we also focus on the latest research progress in the application of electrochemical sensing technology to biologically important compounds’and cancer biomarkers’***,the development trend and challenges of electrochemical sensing technology for in vitro diagnosis are also prospected.

关键词： Electrochemical sensor In vitro diagnosis Biologically important compound cancer biomarker

Advances in liquid biopsy in neuroblastoma

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Fundamental Research 2022年第6期2卷 903-917页

作者： Zhenjian Zhuo Lei Lin Lei Miao Meng Li Jing He Department of Pediatric Surgery Guangzhou Institute of PediatricsGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhou 510623GuangdongChina Laboratory Animal Center School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhen 518055China

Even with intensive treatment of high-risk neuroblastoma(NB)patients,half of high-risk NB patients still *** therapies targeting the biological characteristics of NB have important clinical value for the personalized treatment of ***,the current biological markers for NB are mainly analyzed by tissue *** recent years,circulating biomarkers of NB based on liquid biopsy have attracted more and more *** review summarizes the analytes and methods for liquid biopsy of *** focus on the application of liquid biopsy in the diagnosis,prognosis assessment,and monitoring of ***,we discuss the prospects and challenges of liquid biopsy in NB.

关键词： Liquid biopsy NB Diagnosis Application cancer biomarker