Precise diagnosis and treatment first-the application of biomarkers in precise diagnosis and treatment of diseases NCN2021

The 24th National Neurology Academic Conference of the Chinese Medical Association in 2021 is in full swing.
The "Bojian Neuroscience Summit Forum-Diagnostic Session" on September 24 received extensive attention from participating experts.
This academic session is sincere.
Invite Professor Chen Biao from Xuanwu Hospital of Capital Medical University and Secretary-General Wang Bo of Shanghai Medical Innovation and Development Foundation to serve as chairpersons of the conference, and specially invite Professor Si Lu from Peking University Cancer Hospital, Professor Chen Qin from West China Hospital of Sichuan University, and Su Huadai, Partner of Ernst & Young China Here comes a wonderful theme report
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This article will briefly summarize the wonderful content for readers
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Prof.
Wang Bo, Secretary-General of Shanghai Medical Innovation Development Foundation, Professor Si Lu: The role of biomarkers in disease diagnosis and treatment and basic research is changing Changes in the role of biomarkers
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With the development of detection technology, more and more biomarkers have been developed and applied, laying the foundation for precision treatment.
In recent years, precision treatment is no longer limited to tumor treatment and has entered many other medical fields
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Tailor-made: Biomarkers make precision treatment possible.
The origin of biomarkers can be traced back to the measurement of body temperature and blood pressure hundreds of years ago.
The acceptance and routine use of biomarkers is a very long process.

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With the development of detection technology, more and more biomarkers have been developed (Figure 1)
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Figure 1 Types of biomarkers The development and application of biomarkers has promoted the transformation of clinical diagnosis and treatment models, and provided the possibility for the development of precision therapy (Figure 2)
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Figure 2 Changes in clinical treatment model 2.
General trend: Targeted tumor therapy leads a new era of precision therapy
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Cancer cells often have multiple targets that can be used for treatment, and cancer has become a pioneer in precision therapy .

Among them, the discovery of HER2 gene and EGFR is an important milestone in precision therapy
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So far, the FDA has successively approved multiple biomarker-based treatments such as trastuzumab (HER2), gefitinib (EGFR), and immunotherapy (PD-L1)
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Precision therapy has opened a new era of tumor treatment.
Compared with the chemotherapy era, the 5-year survival rate of different tumors has improved to varying degrees.
In the future, more tumor patients will benefit from biomarker-related precision therapy
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A new era of prosperity: precision treatment surpasses tumors and unlocks more possibilities.
With the continuous deepening of research in various fields, precision treatment can be described as a hundred flowers blooming, detonating a new era of "private customized medical treatment"
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Alzheimer's disease (AD), the largest degenerative disease of the nervous system, is moving towards the era of precision treatment (Figure 3)
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Fig.
3 Precision medicine and Alzheimer’s disease Professor Chen Qin: The application frontier of biomarkers in the field of Alzheimer’s disease Professor Chen Qin from West China Hospital of Sichuan University From clinical symptoms to current biomarker research and AD genetics research, AD has gradually entered a new era of precision medicine
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After a hundred years, Alzheimer's disease has entered the era of biomarkers.
The process of human understanding of AD has spanned a hundred years, and has experienced a long journey from clinical symptoms to biological basis (Figure 4)
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Figure 4 History of AD development ➤At the beginning of the nineteenth century, scientists separated Alzheimer’s disease from other dementias for the first time
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➤In 1905, Alois Alzheimer first discovered the presence of amyloid plaques and neurofibrillary tangles in the brains of AD patients through anatomy
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It was officially named Alzheimer's disease in 1911
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➤Since then, with the development of new research techniques, scientists began to understand the occurrence and development of AD from the genetic level
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In 1991, the AD amyloid hypothesis was formally established and became the most influential hypothesis of the cause of AD in the following 30 years
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➤At present, the number of papers on AD biomarker research has increased sharply in the past 20 years, and biomarker data has become an essential part of AD cohort research (Figure 5)
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The detection of cerebrospinal fluid biomarkers and the development of molecular imaging have opened a new era of AD biomarker research
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Figure 5 Biomarker data has become a necessary component of AD cohort studies 2.
Biomarkers have become an important tool for AD diagnosis and practice of precision medicine.
Without relying on biomarkers, AD misdiagnosis and missed diagnosis are serious
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10%-30% of patients who are clinically diagnosed with AD dementia have no AD pathological changes in autopsy, PET or cerebrospinal fluid (CSF) tests
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Biomarker detection can reduce about 37% of misdiagnosis and 24% of missed diagnosis in the clinical diagnosis of AD-induced mild cognitive impairment (AD-MCI) (Figure 6), improving the accuracy of clinical diagnosis of AD
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Figure 6 ABIDE research results ➤ The development of molecular imaging and the detection of cerebrospinal fluid biomarkers opened a new era of AD biomarker research
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From the invention of the first positron emission tomography (PET) for clinical use in 1953, the FDA approved the first tau PET tracer Tauvid in 2020.
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The development of molecular imaging is the pathology of AD in vivo Detection has opened up a whole new channel
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➤CSF examination is the best source of AD biomarkers, providing a new means for AD diagnosis
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CSF is in direct contact with the extracellular space of the brain, so the biochemical changes in the brain will be reflected in CSF
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Early studies have found that the decline of Aβ42 in CSF may be the earliest marker for identifying preclinical AD
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Newer studies believe that the reduction in the ratio of Aβ42/Aβ40 and Aβ42/Aβ38 may be a better predictor of AD diagnostic biomarkers than Aβ42 alone
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At present, a number of CSF test kits have been approved for marketing in Europe and the United States
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➤The birth of sequencing technology and PCR technology opened the curtain of AD genetics research
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The identification of gene mutations such as APP provides important insights into the molecular mechanism of AD
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Since the launch of the first commercial large-scale sequencer in 2005, the era of high-throughput sequencing (NGS) has been opened
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So far, 37 gene loci have been found to be related to AD, and NGS technology has promoted human cognition of the genetic background of AD (Figure 7)
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Figure 7 The development history of genomics technology ➤The most exciting thing in the AD academic community in recent years is the development of high-sensitivity protein marker detection methods, including mass spectrometry, single-molecule immunoassay, electrochemiluminescence detection, which can detect blood more sensitively Biomarkers in science
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Compared with PET and CSF, blood is easier to obtain and screen, and it is also easier to be accepted by the public
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At present, many studies have tried to use the detection of blood protein markers in the clinic, and it is expected to become an effective means of AD screening in the future (Figure 8)
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Figure 8 The advancement of sequencing, biomedical analysis and big data analysis technology for high-sensitivity protein marker detection methods has promoted the launch of the AD precision medical plan
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Now, biomarkers have become a necessary tool for the diagnosis of AD.
The 2018 European Medicines Agency (EMA) guidelines clearly pointed out that pre-clinical AD is defined as asymptomatic people, and the presence of AD pathology should be measured by biomarkers (Figure 9)
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Figure 9 Changes in AD diagnostic guidelines 3.
Digitization promotes the update of AD to the era of biomarker 2.
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Now is the era of big data, and the emergence of digital analysis tools marks the next level of AD research
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The advancement of artificial intelligence in image segmentation, recognition and classification has further improved the accuracy of AD prediction and diagnosis
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The popularity of consumer-grade wearable devices and mobile devices provides a basis for mining digital biomarkers that predict early AD (Figure 10)
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Figure 10 Digital biomarkers become possible Suhua: Moon landing plan-the industry wave triggered by biomarkers Su Hua, partner of Ernst & Young China, said Su Hua, partner of Ernst & Young China, in the field of diagnostics, both in China and globally, in recent times The field of rapid growth every year is the companion diagnosis that starts with tumors, that is, the use of drugs in conjunction with related targets
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With the development of companion diagnosis, combined with big data in the future, there will be integration of diagnosis and treatment in the field of single disease.
Starting from early inspection and intervention, focusing on the development of the patient's disease, more precise treatment will be given to the patient, and the full cycle of diagnosis and treatment management of the disease will be realized
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For related diseases in the neurological field, in the future, it is also possible to establish a solution for the whole course of disease management by organically linking screening, companion diagnosis and medical device products (Figure 11)
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Figure 11 The neurological disease management center indicates that at the end, Su Hua said that precision diagnosis is never a medical company alone.
It requires testing services, medical institutions, third-party testing centers, reagent companies, diagnostic equipment companies, imaging equipment companies, etc.
to work together to create Ecological, benefiting more patients
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In conclusion, Professor Chen Biao concluded that the diagnosis and treatment of AD has entered a new era, and AD is one of the important diseases affecting the quality of life of the elderly.

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The development of biomarkers makes it possible for us to predict the development direction of the disease at an early stage and intervene early
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Biomarkers make precision treatment possible.
In the future, there will be more and more AD-related biomarkers.
Various indicators have their own advantages and disadvantages.
How to choose may be a factor that needs to be considered in clinical practice
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In short, biomarkers have become a necessary tool to improve the accuracy of clinical diagnosis of AD, and it is expected that the precise treatment of AD will benefit more patients
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