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

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

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Exosomes:Key tools for cancer liquid biopsy

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BIOCELL 2022年第10期46卷 2167-2176页

作者： ISABELLA PANFOLI MAURIZIO BRUSCHI GIOVANNI CANDIANO Dipartimento di Farmacia-DIFAR Universitàdi GenovaGenoa16132Italy Laboratory of Molecular Nephrology IRCCS Istituto Giannina GasliniGenoa16147Italy

Precision medicine is based on the identification of biomarkers of tumor development and *** biopsy is at the forefront of the ability to gather diagnostic and prognostic information on tumors,as it can be noninvasively performed prior or during *** biopsy mostly utilizes circulating tumor cells,or free DNA,but also *** latter are nanovesicles secreted by most cell types,found in any body fluid that deliver proteins,nucleic acids and lipids to nearby and distant cells with a unique homing *** function in signalling between the tumor microenvironment and the rest of the body,promoting metastasis,immune remodelling and drug *** are emerging as a key tool in precision medicine for cancer liquid biopsy,as they efficiently preserve their biomarker ***,exosomes strongly resemble the parental cell,which can help in assessing the oxidative and metabolic state of the donor *** this respect,exosomes represent one of the most promising new tools to fight *** review will discuss the clinical applications of profiling exosomal proteins and lipids by high-throughput proteomics and metabolomics,and nucleic acids by next generation sequencing,as well as how this may allow cancer diagnosis,therapy response monitoring and recurrence detection.

关键词： Cancer Exosome liquid biopsy Precision medicine

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Circulating tumor DNA in liquid biopsy: Current diagnostic limitation

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World Journal of Gastroenterology 2024年第15期30卷 2175-2178页

作者： Shi-Cai Liu School of Medical Information Wannan Medical CollegeWuhu 241002Anhui ProvinceChina

With the rapid development of science and technology,cell-free DNA(cfDNA)is rapidly becoming an important biomarker for tumor diagnosis,monitoring and prognosis,and this cfDNA-based liquid biopsy technology has great potential to become an important part of precision *** is the total amount of free DNA in the systemic circulation,including DNA fragments derived from tumor cells and all other somatic *** cells release fragments of DNA into the bloodstream,and this source of cfDNA is called circulating tumor DNA(ctDNA).cfDNA detection has become a major focus in the field of tumor research in recent years,which provides a new opportunity for non-invasive diagnosis and prognosis of *** this paper,we discuss the limitations of the study on the origin and dynamics analysis of ctDNA,and how to solve these problems in the *** the future faces major challenges,it also con-tains great potential.

关键词： Cell-free DNA Circulating tumor DNA liquid biopsy Cancer Diagnosis Prognosis

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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

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Overview of microRNAs as liquid biopsy biomarkers for colorectal cancer sub-type profiling and chemoresistance

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Cancer Drug Resistance 2021年第4期4卷 934-945页

作者： Alfred Buhagiar Elisa Seria Miriana Borg Joseph Borg Duncan Ayers Faculty of Medicine and Surgery University of MaltaMsida 2080Malta Centre for Molecular Medicine and Biobanking University of MaltaMsida 2080Malta Faculty of medical sciences Newcastle UniversityNewcastle upon Tyne NE17RUUK Faculty of Health Sciences University of MaltaMsida 2080Malta Faculty of Biology Medicine and Health SciencesThe University of ManchesterManchester M139PLUK

Colorectal cancer(CRC)is the third most common cancer *** has also been demonstrated that over the last ten years the incidence of CRC among younger people below the age of 50 is also *** for colorectal cancer is of utmost importance;the rationale behind screening is to target the malignancy and reduce the incidence and mortality of the *** methods to screen for incidence or relapse are therefore a requisite to detect cancer as early as *** findings demonstrate that many deaths are due to lack of screening and therefore early identification will lead to greater *** colorectal cancer,diagnostic tests include liquid biopsy *** the discovery of microRNAs(miRNAs),many studies have demonstrated the relationship between miRNAs and the various sub-types of *** miRNAs have been identified after analysing serum or plasma samples in patients,and such miRNAs were found to be significantly *** findings place the possibility of miRNAs to be at the epicentre of novel diagnostic techniques for CRC identification and sub-type stratification,including other characteristics associated with CRC development such as patient *** following review serves to underline the latest findings for miRNAs with such potential for routine diagnostic employment in CRC diagnostics and treatments.

关键词： MicroRNA miRNA liquid biopsy biomarkers colorectal cancer cancer

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Private somatic mutations identified with liquid biopsy lead tumor progression in solid cancers

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Journal of Cancer Metastasis and Treatment 2020年第1期6卷 718-725页

作者： Maria Palmieri Margherita Baldassarri Nicola Iuso Francesca Fava Alessandra Fabbiani Francesco Cetta Chiara Fallerini Rossella Tita Maria Antonietta Mencarelli Alessandra Renieri Elisa Frullanti Medical Genetics University of SienaSiena 53100Italy Department of Medical Biotechnologies Med Biotech Hub and Competence CenterUniversity of SienaSiena 53100Italy Genetica Medica Azienda Ospedaliera Universitaria SeneseSiena 53100Italy

Aim:Primary tumors can be divided into oncogene-addicted(e.g.,lung)and non-oncogene addicted(e.g.,breast).Only the former group has an Achilles-heel single gene for successful target therapy,whereas the latter has mutations of multiple causative ***,tissue biopsy used for genetic surveys do not give a complete picture of the molecular profile and clonal evolution,but only provide static information over ***:A series of 133 patients with 16 different solid tumors were *** samples were collected and cell-free DNA(cfDNA)was *** libraries were analyzed using AVENIO circulating tumor DNA(ctDNA)Expanded Kit and Illumina NextSeq 550 for sequencing was *** order to evaluate the clinical evolution over time,a second cfDNA analysis was performed after a mean interval of 2 ***:Through the cfDNA liquid biopsy,we found 89 pathogenic variants in 54 ***,lung,and prostate cancers showed the largest number of mutated ***53,PIK3CA,FGFR3,KRAS,and ERBB2 were the most frequently mutated genes among 16 different *** distribution didn’t show any type of *** particular,every patient with disease progression seems to have a“private”combination of gene pair mutations,with TP53 as the most frequently mutated ***:We showed that the clonal evolution of tumors includes a private combination of genes,regardless of tumor *** the future,the cancer treatment can be the targeted therapy against specific tumor mutation(s).The present approach seems promising to both identify key cancer genes and follow clonal evolution over time.

关键词： Cell-free DNA liquid biopsy solid tumors advanced tumors private mutations targeted-therapy

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Circulating microRNAs and liquid biopsy:murine xenograft models for technical validation of clinical protocols

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Journal of Cancer Metastasis and Treatment 2019年第6期4卷 87-97页

作者： Jessica Gasparello Matteo Allegretti Chiara Papi Elena Giordani Patrizio Giacomini Roberto Gambari Alessia Finotti Department of Life Sciences and Biotechnology Ferrara UniversityFerrara 44121Italy Oncogenomics and Epigenetics IRCCS Regina Elena National Cancer InstituteRome 00144Italy Interuniversity Consortium for Biotechnology(CIB) Trieste 34149Italy

In oncology,liquid biopsy is applied to detect with high efficiency clinically relevant analytes,such as tumor cells,cell-free nucleic acids,and exosomes in peripheral blood and other body fluids of cancer *** biopsy is considered one of the most advanced non-invasive diagnostic systems useful,in the next future,for enabling personalized treatments in precision *** actions include,but are not limited to,early diagnosis,staging,prognosis,anticipation(lead time)and prediction of therapy responses,as well as follow *** system for validation of the proposed liquid biopsy approaches is highly *** this review article we will discuss the establishment of xenotransplanted mouse model systems for the validation of liquid biopsy protocols aimed to identify changes in the miRNA plasma *** colon cancer HT-29 and LoVo cells have been xenotransplanted and miR-221-3p and miR-222-3p have been comparatively analyzed in cultured HT-29 and LoVo cells,xenotransplants and plasma samples.

关键词： liquid biopsy circulating tumor RNA microRNA xenograft

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Exosomal lncRNAs: the newest promising liquid biopsy

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Cancer Drug Resistance 2019年第4期2卷 1002-1017页

作者： Marta Tellez-Gabriel Dominique Heymann RNA and Molecular Pathology(RAMP)Research Group Department of Medical BiologyThe Artic University of Norway(Tromso)Tromso 9019Norway INSERM Institut de Cancérologie de l’OuestLabCTU1232CRCINAUniversitéde NantesUniversitéd’AngersSaint Herblain 44805France

LncRNAs are defined as RNA transcripts greater than 200 nucleotides in length that have no or limited protein-coding *** expression of lncRNAs appeared important for various homeostatic processes,like gene imprinting cell differentiation and ***,it has been demonstrated that lncRNAs play an important role in tumorigenesis and *** lncRNAs were stably detected in exosomes,which are widely found in body *** studies validated the use of exosomal lncRNAs as minimally invasive diagnostic and prognostic markers in several types of *** addition,exosomal lncRNAs have been associated with drug resistance of tumor cells,suggesting a clinical application in cancer-targeted *** the recent increase of studies on exosomal lncRNAs,their clinical significance in cancer diagnosis,prognosis and treatment needs to be fully *** methodologies for their detection with high purity and accuracy must be also improved in order to implement their use in clinical *** review aims to summarize the main recent technologies available for the isolation of exosomal lncRNAs,their status as a liquid biopsy as well as their future perspectives.

关键词： liquid biopsy long non-coding RNAs exosomes

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The use of liquid biopsy in early breast cancer:clinical evidence and future perspectives

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 33-48页

作者： Paolo D’Amico Carla Corvaja Lorenzo Gerratana Carolina Reduzzi Giuseppe Curigliano Massimo Cristofanilli Division of Hematology and Oncology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoIL 60611USA Division of Early Drug Development for Innovative Therapies IEOEuropean Institute of Oncology IRCCSMilan 20132Italy Department of Oncology and Hemato-Oncology University of MilanoMilan 20122Italy Department of Oncology ASUFCUniversity Hospital of UdineUdine 33100Italy Department of Medicine University of UdineUdine 33100Italy Department of Medical Oncology Centro di Riferimento Oncologico(CRO)IRCCSPordenone 33081Italy

liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is gaining momentum as a diagnostic modality adopted in the clinical management of breast *** studies testing several technologies demonstrated clinical validity and,in some cases,achieved the United States Food and Drug Administration *** initial testing and clinical application of liquid biopsy focused primarily on the diagnosis,while molecular characterization and monitoring of metastatic disease,with larger data from prospective studies,came in the last two *** its role in metastatic setting is thus widely recognized,the current evidence does not provide support for the routine clinical use of liquid biopsy methods for the earlier stage of this *** the relevance of early detection,characterization,and management of breast cancer in the early-stage,this clinical setting is the most suitable to increase the chances for effective treatment selection and improved prognosis,and a better understanding of the main application of liquid biopsy tools in the earlier stage of breast cancer is therefore *** aim of this review is to provide an overview of the clinical evidence and subsequent potential applications of liquid biopsy in early breast cancer,identifying the main existing caveats and the possible future scenarios.

关键词： liquid biopsy early breast cancer circulating tumor cells circulating tumor DNA clinical trials screening early detection minimal residual disease

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liquid biopsy in ovarian cancer:Catching the silent killer before it strikes

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World Journal of Clinical Oncology 2020年第11期11卷 868-889,I0002页

作者： Laura Feeney Ian JG Harley W Glenn McCluggage Paul B Mullan James P Beirne Patrick G Johnston Centre for Cancer Research Queens UniversityBelfast BT97AEUnited Kingdom Northern Ireland Gynaecological Cancer Centre Belfast Health and Social Care TrustBelfast BT97ABUnited Kingdom Department of Pathology Belfast Health and Social Care TrustBelfast BT126BLUnited Kingdom Trinity St James Cancer Institute St.James’HospitalDublin 8Ireland

Epithelial ovarian cancer(EOC)is the most lethal gynaecological malignancy in the western *** majority of women presenting with the disease are asymptomatic and it has been dubbed the“silent killer”.To date there is no effective minimally invasive method of stratifying those with the disease or screening for the disease in the general *** molecular and pathological discoveries,along with the advancement of scientific technology,means there is a real possibility of having disease-specific liquid biopsies available within the clinical environment in the near *** this review we discuss these discoveries,particularly in relation to the most common and aggressive form of EOC,and their role in making this possibility a reality.

关键词： Epithelial ovarian cancer Molecular profile liquid biopsy Circulating tumor DNA Biomarker discovery Precision medicine

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