2021CSCO's wonderful companion diagnosis-based on innovative technology to achieve precise diagnosis and treatment

Introduction During the 2021 CSCO General Assembly to "precision | see 'micro' know the, proud 'melt' 'companion diagnostic tumor-themed concert was successfully held on September 28
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Under the leadership of Professor Wu Yilong from Guangdong Provincial People’s Hospital, Professor Lu Shun from the Chest Hospital of Shanghai Jiaotong University, and Professor Wang Jie from the Cancer Hospital of the Chinese Academy of Medical Sciences, Professor Yang Fan from Peking University People’s Hospital, Professor Jiang Guozhong from the First Affiliated Hospital of Zhengzhou University, and West China from Sichuan University Many clinical experts such as Professor Wang Yongsheng from the hospital gathered to share the latest technical progress and breakthroughs in multiple clinical pain points, such as the detection of minimal residual disease (MRD), DNA+RNA double fusion detection, and liquid biopsy PD-L1 expression detection
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Extremely advanced, composing MRD detection Xinhua Chapter MRD is considered to be the root cause of postoperative tumor recurrence, but it is difficult to be detected by existing detection methods including traditional imaging, serology and pathology.
The clinic urgently needs to be convenient, non-invasive, and direct.
A new diagnostic method that reflects the status of the tumor and provides information on the progress of the tumor
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A number of research data have shown that the detection of MRD by ctDNA has potential application value and has the feasibility of application in multiple tumor types
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However, there are three technical challenges in detecting MRD by ctDNA: (1) Not all tumors release detectable ctDNA; (2) ctDNA is low in abundance and metabolized quickly; (3) clonal hematopoietic mutation interference
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Therefore, detection of MRD based on ctDNA puts forward higher requirements on the sensitivity of the technology
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How to improve the sensitivity of ctDNA detection? Extending the detection range, increasing the sequencing depth, increasing the detection frequency, and the amount of blood collected are conventionally available methods, but there are limitations in clinical applications, and it is difficult to fundamentally solve the sensitivity problem
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International studies represented by CAPP-Seq, TRACERx, and MRDetect have provided references for everyone in different directions
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As technology continues to be explored, clinical application issues, such as the best time for postoperative testing, also need to be answered
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A Dynamic study, jointly conducted by the team of Academician Wang Jun of Thoracic Surgery Department of Peking University People's Hospital and Herui Gene, was published in Clinical Cancer Research in 2019.
This study is the world's first prospective assessment of the dynamic changes of ctDNA during the perioperative period.
Sex research is also the first research in Asia to use ctDNA to monitor MRD after lung cancer surgery
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The study used the cSMART technology independently developed by Herui Gene to prospectively evaluate the metabolism of ctDNA after complete resection, and found that the half-life of ctDNA is about half an hour, and 3 days after surgery can be used as the best time for postoperative MRD monitoring.
Point
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The study was published online for only two weeks, and it was listed as a highlight study by Nature Reviews Clinical Oncology, with a special review
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Based on the Dynamic research, Herui Gene continued to cultivate and explore the optimization plan for MRD detection, and launched the solid tumor MRD detection program during the CSCO period-Hezhuan, which is specially designed and developed for patients with solid tumors during the perioperative period, and can be used for dynamic assessment of the surrounding area.
The status of the MRD during the operation indicates the risk of recurrence after the operation of the patient.
At the same time, it can provide reference information for medication treatment and prognosis prediction, and help the patient's entire course of disease management
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Advantages of Hezhuan detection program This detection program firstly detects the solid tumor large panel gene of the patient's tumor tissue to obtain the patient's gene mutation map, and at the same time provides targeted, chemotherapy, and immune drug prompts for the patient's neoadjuvant/adjuvant therapy
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Then, based on the exclusive MRD detection panel, the postoperative plasma samples are monitored dynamically at multiple time points and with ultra-high sensitivity to help patients find disease recurrence early and improve the survival benefits of patients
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Regarding the direction of detecting MRD through ctDNA, Professor Yang Fan from Peking University People’s Hospital said: Technological innovation has helped MRD detection achieve more breakthroughs.
Innovative technology companies represented by Herui Gene are no longer inferior to foreign technologies in terms of technology.

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It is hoped that the MRD detection technology can be more mature and be verified by clinical application value, so as to completely change the clinical dilemma of patients who cannot choose postoperative adjuvant treatment and cannot evaluate the efficacy
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Overcome difficulties and set off a new era of DNA+RNA fusion gene detection.
The MRD detection program for solid tumors provides a reliable way for postoperative recurrence risk detection and adjuvant therapy patient identification, and provides an information reference for precise tumor treatment
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Targeted drugs are another important method for precise tumor treatment.
How to understand the mystery of gene fusion detection has become one of the current hot research directions
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Gene fusion is not an accidental event, it occurs in a variety of solid tumors
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An article published in Cell in 2018 showed that among 9624 samples, 16.
5% of patients had gene fusions and 6% of patients had medication-related fusions
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With the deepening of research and the development of targeted drugs, the importance of accurate detection of fusion genes has become more and more prominent, and has become a prerequisite for accurate drug use and benefits for patients
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The current technologies for detecting gene fusion include: fluorescence in situ hybridization (FISH), next-generation gene sequencing (NGS), reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry (IHC), each of which has its own advantages Among them, NGS has high throughput and can detect fusion genes, known or unknown genes at the DNA and RNA levels.
It is currently recognized as the best platform for clinical fusion gene detection
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Fusion can occur not only at the DNA level, but also at the RNA level
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Gene fusion mechanisms at the DNA level include ectopic intra/inter chromosome, insertion or deletion of large fragments, etc.
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At the RNA level, the "read-through event" during the transcription process may also produce fusion proteins.
Since the fusion does not involve rearrangement at the DNA level, it cannot be found by DNA level analysis
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In actual clinical applications, there are two strategies for DNA-RNA sequential detection and DNA+RNA parallel detection
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Compared with the sequential strategy, DNA+RNA parallel detection, while overcoming the limitations of single DNA or single RNA, can maximize the detection of fusion, save samples and time, which is more beneficial to patients
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Professor Jiang Guozhong from the First Affiliated Hospital of Zhengzhou University shared the research results of his cooperation with Herui Gene at the meeting
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The research utilizes Herui Gene's cutting-edge technology, and optimizes the probe design based on the recommended detection mode of non-small cell lung cancer NCCN guidelines-DNA+RNA parallel NGS method to detect gene fusions, so that the DNA-panel probes cover common fusions In the intron region of the partner gene, 14 complicated ALK rearrangements of 3 types were successfully identified
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Professor Jiang Guozhong pointed out that both DNA testing and RNA testing have limitations and challenges in actual clinical practice.
DNA+RNA parallel testing can detect fusion genes more effectively
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Herui Gene is an excellent molecular diagnostic platform introduced by the First Affiliated Hospital of Zhengzhou University.
It has continued to innovate and optimize in terms of innovative products and technology development.
The extraction and database construction system can ensure that 92% of the samples achieve double detection of DNA+RNA
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At the same time, in order to maximize DNA fusion detection, Herui Gene designs probes for the fusion gene and the partner gene at the same time, increases the probe coverage density, and continues to optimize the capture strategy for difficult areas such as the 31 intron region of the ROS1 gene.
, And independently developed the SVscan® algorithm, relying on these original technologies and optimized detection systems to achieve fusion high-precision detection
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In the more difficult and in-depth exploration of the use of liquid biopsy for fusion detection, Herui Gene continues to innovate in technology and independently research and develop SpCap cfRNA technology to break the technical bottleneck, which can achieve more convenient and rapid extraction of cfRNA, more efficient and stable database construction and target genes Enrichment and detection performance help truly realize DNA+RNA fusion detection
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In the future, Herui Gene will continue to explore the performance of SpCap cfRNA technology in cerebrospinal fluid, saliva, and alveolar lavage fluid
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Herui Gene DNA+RNA Blood Test SpCap Technology "The development of cfRNA-based fusion technology is expected to realize the dual detection of DNA+RNA in the blood
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With the continuous R&D and innovation of excellent enterprise technologies such as Herui Gene , the fusion detection and the The understanding of integration will be deeper and deeper, and diagnosis and treatment will become more and more accurate
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” Professor Jiang Guozhong commented
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For the benefit of patients, explore new solutions for liquid biopsy level PD-L1 expression detection.
The information hidden in genes not only guides the application of targeted therapy, but also provides a "key" for the precise identification of people who benefit from immunotherapy
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The advent of immunotherapy has changed the treatment pattern of multiple tumor types and brought long-term survival benefits to patients
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Similar to targeted therapy, how to make more precise immunotherapy decisions? Become one of the key directions of clinical research at the current stage
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Different from targeted therapy, the determination of an immunotherapy plan needs to be considered from multiple dimensions, such as tumor cells, tumor microenvironment, peripheral circulation factors, adverse reactions, and super-progress
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Among them, the expression of programmed death ligand 1 (PD-L1) is one of the most widely used and most accessible immunotherapy markers in clinical practice, providing reliable guidance for the formulation of clinical treatment strategies
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Although PD-L1 detection is widely used, there are still many challenges, such as the diverse standards of the PD-L1 immunohistochemical detection platform and the temporal and spatial heterogeneity of PD-L1 expression, which can affect the predictive value of PD-L1 detection
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In addition, a large number of clinical patients have the problem of tissue inaccessibility, and it is difficult to achieve PD-L1 immunohistochemical detection
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Is it feasible to detect PD-L1 expression by liquid biopsy? With the in-depth exploration of the PD-L1 gene, many studies have shown that the 3'UTR mutation of the PD-L1 gene can well predict the efficacy of immunotherapy and is a potential biomarker
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The PD-L1 gene is located on chromosome 9 and has 7 exons, which form mRNA through transcription
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The mRNA level is mainly regulated by microRNA, and the 3'UTR of PD-L1 gene can bind to microRNA to promote mRNA degradation
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The 3'UTR mutation of the PD-L1 gene affects microRNA binding and leads to the up-regulation of PD-L1 expression
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In clinical applications, there are many challenges in the detection of 3'UTR mutations in the PD-L1 gene: (1) Conventional panel design only covers mutation hot spots or exon regions, and the importance of the 3'UTR region of the gene is often ignored; (2) ) PD-L1 gene 3'UTR destructive mutations are often structural mutations, which are difficult to cover probes and biometric analysis; (3) For liquid biopsy samples, ctDNA content is low and fragmentation is serious, making it more difficult to detect structural mutations Big
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The three "big mountains" lie on the path of gene structure mutation detection, and put forward higher requirements for both probe design and biometric algorithms
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Optimizing probe design, performing DNA+RNA dual detection, and developing a biometric algorithm for 3'UTR structural variation are ways to break through the dilemma of the existing technology
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In this regard, Herui Gene, a representative domestic tumor whole-course management genetic testing company, has optimized the probe coverage and capture strategy, using its advantages in the field of DNA+RNA dual detection for many years, and used the self-developed SVscan® patent algorithm.
, "Meeting" the challenge of gene structure variation detection
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Professor Wang Yongsheng from West China Hospital of Sichuan University introduced that in clinical practice, Herui Gene's Hequan-Solid Tumor Whole Target Gene Detection (654 gene) product has found 7 cases of PD-L1 gene 3'UTR structural variation, including There are three types of intrachromosomal translocation, chromosomal deletion, and interchromosomal translocation, and the consistency of blood ctDNA and tumor tissue DNA detection reaches 100%
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In addition, the copy number change of the PD-L1 gene also has good predictive value
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He Quan'an-solid tumor full target gene detection (654 genes) product adopts multi-dimensional PD-L1 detection strategy, in addition to immunohistochemical PD-L1 protein expression level detection, PD-L1 gene copy number will also be performed at the same time Mutation detection and PD-L1 gene 3'UTR region detection to help achieve better immunotherapy guidance
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The Herui Gene 654 Panel has the advantages of PD-L1 multi-dimensional detection.
It is expected that in the future, the PD-L1 multi-dimensional detection including the copy number variation of the PD-L1 gene and the detection of the destructive variation of the 3′UTR region can become a convenient clinical use.
Liquid biopsy level is one of the detection methods of PD-L1 expression, so as to help patients with inaccessible tissues to predict PD-L1 expression level and achieve precise immunotherapy
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With a number of innovative research, independent research and development of leading technologies, and continuous ground-breaking products, Herui Gene has further consolidated its position as a leader in gene detection for the whole course of cancer in China
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Professor Lu Shun from the Chest Hospital of Shanghai Jiaotong University stated that the theme of the Herui Gene Companion Diagnosis Workshop is closely linked to the theme of the CSCO conference "Focus on Innovative Research, Leading the Original Future"
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The field of precision diagnosis is the forefront of Herui Gene's foothold.
Herui Gene has realized true DNA+RNA double fusion detection, which significantly improves the detection accuracy of fusion genes and enables more patients to receive precise treatment
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Herui Gene's achievements in innovative research and leading the original field are obvious to all.
We hope that Herui Gene's data will trigger more thinking and practice on tumor diagnosis and treatment
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