What you need to learn from Liquid Biopsy?

I. Liquid biopsy is a concept corresponding to traditional tissue biopsy. It is an in vitro diagnostic technique for sampling and analyzing non-solid biological tissues such as blood. The “liquid” in liquid biopsy are mainly blood, including feces, urine, saliva and other body fluid samples. The most important application of liquid biopsy are early screening, diagnosis, medication guidance, monitoring, prognosis management, and non-invasive prenatal detection. In addition, it also includes musculature system , connective tissue, infectious and parasitic diseases.

Compared with traditional tissue biopsy, one of the advantages of liquid biopsy is that it can reflect the comprehensive information of the lesions. Precise treatment is based on gene analysis of tissue samples from tumors and other lesions. The traditional methods are surgical biopsy and puncture biopsy. Because of the strong heterogeneity of tumor cells, traditional methods can only obtain samples. The genetic information of location can not reflect the comprehensive information of tumors as a whole. The second advantage is that it can be monitored at high frequency. Gene changes in cancer cells may lead to drug resistance. High frequency monitoring is necessary to achieve accurate drug use. Liquid biopsy can be achieved by simple intravenous blood sampling, which can meet the needs of high frequency monitoring. The third advantage is that it can significantly reduce the cost and risk of patients. The cost of lung biopsy is several times higher than that of liquid biopsy, and there is a greater risk of complications.

II. It is because of the irreplaceable technical advantages of liquid biopsy that it has brought broad market prospects.

China have many policies and events in supporting for liquid biopsy technology: The Ministry of Science and Technology proposed to invest 60 billion RMB in precise medical treatment before 2030; The Health Planning Commission “Notice of the Medical Administration of the National Health and Family Planning Commission on the Pilot Work of Clinical Application of High Throughput Gene Sequencing Technology for Tumor Diagnosis and Treatment Project”; Ministry of Health “Notice on Preliminary Research on Indoor Quality Assessment of Tumor Diagnosis and Treatment by High-throughput Sequencing Testing (Multi-gene Detection)”; Medical Planning Commission “Technical Guidelines for Gene Detection of Drug Metabolic Enzymes and Drug Targets (Trial Implementation)” and “Technical Guidelines for Individualized Tumor Therapy Monitoring (Trial Implementation)”; Development and Reform Commission “About the First Batch of Bases” Reply to the Construction Plan of the Demonstration Center for Detection Technology Application. At present, the clinical access of liquid biopsy products in China can be achieved in two ways (similar to FDA+CLIA dual channel in the United States). One is through CFDA approval for listing; the other is as a self-built laboratory project (LDTs) used in medical laboratories approved by the Health and Planning Commission, which is not restricted by CFDA registration of instruments and reagents. It is more rapid and widely used by many gene testing companies.

III. How is the development of liquid biopsy?

The following branches of liquid biopsy have been developed according to the different detectors:

1.CTC technology: Circulating Tumor Cell (CTC) is a tumor cell that is free from the blood circulation system. It is derived from the primary tumor tissue and is an important way of tumor cell metastasis. It is an important factor for recurrence and mechanism of cancer death. As a tumor cell, CTC not only contains the DNA information of the tumor, but also contains information such as genome and proteome, which is a rich source for studying tumor tissue information.

2.cfDNA/ctDNA technology: Cell-free DNA (cfDNA) is a DNA fragment derived from cells that is free from the blood circulatory system. It is mainly derived from DNA fragmentation, DNA fragments of necrotic cells, and cell secretion. The most important class of cfDNA is Circulating Tumor DNA (ctDNA), a DNA fragment from the tumor genome that enters the blood circulatory system, carrying mutations, insertions, deletions, rearrangements, copy number abnormalities and/Or methylation and other genetic information.

3.Exosomes: Exosome is a vesicle secreted by cells. The vesicles contain proteins, DNA, messenger RNA and some non-coding RNAs. They are the carriers of communication between cells, and the occurrence and development of tumors. There is a correlation between metastasis and drug resistance. Tumor cells use these vesicles as carriers to help them escape the surveillance of the immune system. These vesicles guide the direction of tumor cell migration and create a micro environment suitable for tumor growth.

4.Circulating RNA technology: Circulating RNA is extracellular RNA present in blood or other body fluids, mainly mRNA, miRNA and other types of RNA, which are closely related to cellular metabolism under physiological and pathological conditions. Clinical research focuses on prenatal diagnosis and early diagnosis of tumors.

IV. What are the advantages and disadvantages of various types of liquid biopsy?

In practice, because of the large number of CTC patients in the advanced stage of cancer and the small number of patients in the early stage, the current major clinical application is limited to predicting the prognosis by detecting the number of CTCs in postoperative or advanced patients. The most mature application of cfDNA is NIPT (non-invasive prenatal genetic testing). The analysis of fetal free blood by analyzing venous blood of pregnant women to determine the probability of fetal suffering from Down syndrome has become a common screening method for prenatal and postnatal education in China. The most common application of ctDNA is to drive gene detection, such as peripheral blood EGFR mutation detection, to provide a basis for medication guidance. Exosomes and circulating RNA are still in the early stage of research, and there are few practical applications.

In general, CTC technology and cfDNA technology research is more abundant, practical applications are more, and the understanding of its advantages and defects is more mature and comprehensive. Among them, CTC technology started earlier and clinical research is more abundant, but the development of this technology is limited by the characteristics of high technical difficulty, low detection rate and strong heterogeneity. Especially the separation of CTC is very difficult, and it can not meet the needs of clinical examination. Compared with CTC, ctDNA capture is relatively easy, and detection methods are more mature. Although ctDNA enrichment still has bottlenecks, it can meet some detection needs of patients with advanced cancer, give valuable diagnostic opinions, and ctDNA is The detection of gene mutations is uniquely advantageous, and thus more and more applied to the treatment guidance and monitoring of cancer. In recent years, the focus of corporate and capital on liquid biopsy has shifted from CTC to ctDNA, which has become the most commonly used in the market. Liquid biopsy technology. In addition, with the large-scale investment of some companies such as SANLI MEDICAL in the field of ctDNA technology, the number of clinical research and trials will increase rapidly, and the problem of early screening of cancer may also be solved. In addition, ctDNA has also been found to have potential applications in another popular technology for tumor immunotherapy, which can be used to guide immunotherapy or predict the efficacy of immunotherapy.