Liquid Biopsy in Coronary Heart Disease.

Cardiovascular disease (CVD) remains the major cause of morbidity and mortality globally. Accumulating evidence indicates that coronary heart disease (CHD) contributes to the majority of cardiovascular deaths. With the development of precision medicine, the diagnosis and treatment of coronary heart disease are becoming more refined and individualized. Molecular diagnosis technology and individualized treatment are gradually applied to the clinical diagnosis and treatment of CHD. It is great significance to seek sensitive biological indicators to help early diagnosis and improve prognosis of CHD. Liquid biopsy is a minimally invasive technique, which is widely used to detect molecular biomarkers of tumors without invasive biopsy. Compared with the field of oncology, it is not easy to get the diseased tissue in CVD, especially CHD. Therefore, the idea of "fluid biopsy" is very attractive, and its progress may provide new and useful noninvasive indicators for CHD. By analyzing circulating cells or their products in blood, saliva, and urine samples, we can investigate the molecular changes that occur in each patient at a specific point in time, thus continuously monitoring the evolution of CHD. For example, the assessment of cell-free DNA (cfDNA) levels may help predict the severity of acute myocardial infarction and diagnose heart transplant rejection. Moreover, the unmethylated FAM101A gene may specifically track the cfDNA derived from cardiomyocyte death, which provides a powerful diagnostic biomarker for apoptosis during ischemia. In addition, the changes of plasma circulating miR-92 levels may predict the occurrence of acute coronary syndrome (ACS) onset in patients with diabetes. Liquid biopsy can reflect the disease state through patients' body fluids and may noninvasively provide dynamic and rich molecular information related to CHD. It has great application potential in early warning and auxiliary diagnosis, real-time monitoring of curative effect, medication guidance and exploration of drug resistance mechanism, prognosis judgment, and risk classification of CHD. This chapter will review the latest progress of liquid biopsy in accurate diagnosis and treatment of CHD, meanwhile explore the application status and clinical prospect of liquid biopsy in CHD, in order to improve the importance of precision medicine and personalized treatment in this field.

Zhu W ，Li X 《-》

Fluid-based assays and precision medicine of cardiovascular diseases: the 'hope' for Pandora's box?

Progresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field.

Benincasa G ，Mansueto G ，Napoli C 《-》

Liquid biopsy in CNS tumors: Current status & future perspectives.

Husain N ，Husain A ，Mishra S ，Srivastava P ... -  《-》

Liquid biopsy: current technology and clinical applications.

Liquid biopsies are increasingly used for cancer molecular profiling that enables a precision oncology approach. Circulating extracellular nucleic acids (cell-free DNA; cfDNA), circulating tumor DNA (ctDNA), and circulating tumor cells (CTCs) can be isolated from the blood and other body fluids. This review will focus on current technologies and clinical applications for liquid biopsies. ctDNA/cfDNA has been isolated and analyzed using many techniques, e.g., droplet digital polymerase chain reaction, beads, emulsion, amplification, and magnetics (BEAMing), tagged-amplicon deep sequencing (TAm-Seq), cancer personalized profiling by deep sequencing (CAPP-Seq), whole genome bisulfite sequencing (WGBS-Seq), whole exome sequencing (WES), and whole genome sequencing (WGS). CTCs have been isolated using biomarker-based cell capture, and positive or negative enrichment based on biophysical and other properties. ctDNA/cfDNA and CTCs are being exploited in a variety of clinical applications: differentiating unique immune checkpoint blockade response patterns using serial samples; predicting immune checkpoint blockade response based on baseline liquid biopsy characteristics; predicting response and resistance to targeted therapy and chemotherapy as well as immunotherapy, including CAR-T cells, based on serial sampling; assessing shed DNA from multiple metastatic sites; assessing potentially actionable alterations; analyzing prognosis and tumor burden, including after surgery; interrogating difficult-to biopsy tumors; and detecting cancer at early stages. The latter can be limited by the small amounts of tumor-derived components shed into the circulation; furthermore, cfDNA assessment in all cancers can be confounded by clonal hematopoeisis of indeterminate potential, especially in the elderly. CTCs can be technically more difficult to isolate that cfDNA, but permit functional assays, as well as evaluation of CTC-derived DNA, RNA and proteins, including single-cell analysis. Blood biopsies are less invasive than tissue biopsies and hence amenable to serial collection, which can provide critical molecular information in real time. In conclusion, liquid biopsy is a powerful tool, and remarkable advances in this technology have impacted multiple aspects of precision oncology, from early diagnosis to management of refractory metastatic disease. Future research may focus on fluids beyond blood, such as ascites, effusions, urine, and cerebrospinal fluid, as well as methylation patterns and elements such as exosomes.

Nikanjam M ，Kato S ，Kurzrock R 《Journal of Hematology & Oncology》

Cell-Free DNA, MicroRNAs, Proteins, and Peptides as Liquid Biopsy Biomarkers in Prostate Cancer and Bladder Cancer.

Liquid biopsy, as a novel noninvasive tool for biomarker discovery, has gained a lot of attention and represents a significant innovation in precision medicine. Due to its minimally invasive nature, liquid biopsy has fewer complications and can be scheduled more frequently to provide individualized snapshots of the disease at successive time points. This is particularly valuable in providing simultaneous measurements of tumor burden during treatment and early detection of tumor recurrence or drug resistance. Blood-based liquid biopsy is an attractive, minimally invasive alternative, which has shown promise in diagnosis, risk stratification, disease monitoring, and more. Urine has gained popularity due to its less invasive sampling, the ability to easily repeat samples, and the ability to track tumor evolution in real time, making it a powerful tool for diagnosis and treatment monitoring, especially in urologic cancers. In this review, we provide a detailed discussion on the potential clinical applications of prostate cancer (PCa) and bladder cancer (BCa), with cell-free DNA (cfDNA), microRNAs (miRNAs), proteins, and peptides as liquid biopsy biomarkers.

Chen H ，Xu C ，Fang Z ，Mao S ... -  《-》