The significance of biomarkers for tumor transformation medicine: from screening, confirmation to clinical application

The significance of biomarkers for tumor transformation medicine: from screening, confirmation to clinical application
Chi Ming, Product Specialist, Department of Life Sciences, GE Healthcare
Whether medicine can effectively treat and cure cancer depends directly on whether it can be detected in the early stages of cancer. As the most direct and effective diagnostic tool, biomarkers can play an important role in the diagnosis, development, treatment, and efficacy monitoring of tumors. Therefore, since the introduction of this concept, it has received great attention and become a hot spot and focus of research. These biomarkers can be methylation of DNA, templates with single nucleotide polymorphisms (SNPs), changes in protein or metabolism, changes in mRNA, etc., and these changes are closely related to the occurrence of disease states in the body. A variety of technology platforms have been applied to biomarker research, such as omics platforms including genomics, proteomics, peptideomics, metabolomics, and nanotechnology [1], bioinformatics [2], antibody chip [3], high-content screening technology [4], label-free interaction analysis technology [5] and other cutting-edge technologies and methods, all for the rapid acquisition and screening of biomarkers Great possibility.
The advantages of proteomics offer hope for screening biomarkers in the early stages of tumors, which can be used for early diagnosis, prediction, and monitoring of disease progression. This discipline integrates technologies that can analyze complex biological systems such as 2-DE, 2D-DIGE, ICAT, iTRAQ, protein chips, MudPIT and mass spectrometry. These techniques can obtain a variety of physiological and pathological changes in information from the omics level. These techniques can be used to comprehensively discover changes in tumor-associated biological mechanisms to obtain new diagnostic test markers to improve treatment outcomes. [6]
Oncoproteomics, a discipline that uses proteomics to study proteins and their interacting molecules in tumor cells. With the rapid development of mass spectrometry and protein chip technology, more and more proteomics research has been used in tumor research. Oncoproteomics has the potential to revolutionize clinical practice, including proteomics-based tumor diagnosis and screening platforms as a complementary discipline of histopathology, personalized choices for treatment strategies for specific cancer-associated specific protein networks, real-time therapeutic effects and Monitoring and evaluation of toxicity, as well as changes in tumor protein network based on prognosis and resistance, rationally regulate treatment. In addition, Oncoproteomics has also been used to find new therapeutic targets and drug action sites. With the opening of the post-genome era, Oncoproteomics research provides people with a better understanding of the opportunities for tumorigenesis. [7]
2-DE is the first method used by proteomics to screen biomarkers and is one of the most widely used methods. The introduction of 2D-DIGE has made this traditional method a new life. Biomarkers that are currently available for diagnosis by 2-DE or 2D-DIGE methods involve a variety of diseases such as bladder cancer [8], rectal cancer [9], esophageal cancer [10], gastric cancer [11], Liver cancer [12], lung cancer [13], nasopharyngeal carcinoma [14], ovarian cancer [15], pancreatic cancer [16], prostate cancer [17] and so on. Recently, Buhimschi et al. reported the use of the 2D-DIGE method to identify 19 significantly differentially expressed proteins in cord blood samples from children with neonatal sepsis, which were further screened and confirmed by multiplex assays to bind haptoglobin. Expression has been shown to be associated with neonatal sepsis caused by prenatal amnion infection and/or inflammation [18]. As a potential biomarker with "switching effect" in cord blood, Haptoglobin provides a fast and effective means for screening neonatal sepsis and has great application prospects.
In addition, there are a variety of methods for the screening of biomarkers, such as the use of ICAT combined tandem mass spectrometry to obtain biomarkers for breast cancer diagnosis [19], immunoblot and tissue microarray analysis to obtain biomarkers for rectal cancer diagnosis. [20], using tissue MALDI-TOF MS method to obtain biomarkers for glioma diagnosis [21], using DotScan chip (clustering of differential antibody chips) to study leukemia biomarkers [22], using two-way sequence Cluster analysis to study lymphoma biomarkers [23] and so on.
As proteomics technology matures, the number of biomarkers obtained using omics technology is increasing, and problems and challenges coexist. Although a large number of biomarkers have been discovered, only a few have been clinically recognized and approved by the US FDA, and most have no clinical value. The reason for this is that the lack of some standard techniques and methods for the evaluation and confirmation of the obtained biomarkers to determine the clinical value of the resulting markers, to help improve the efficiency and quality of conversion from research to clinical. For such needs, discovery, verification and qualification become standard processes commonly used to obtain high quality biomarkers. [24] Conventional methods for verification and quantification include ELISA, etc. However, with the development of technology and the requirements for high throughput and accuracy, these technologies often fail to meet current needs. Therefore, more emerging technologies such as MRM-MS and Biacore have begun to show their talents, which has injected a strong impetus to accelerate the confirmation of biomarkers and improve the efficiency of scientific research to clinical transformation.
Taking Biacore as an example, this SPR-based non-marker technology has been a tool for researchers to obtain information on interactions between biomolecules for more than a decade. Information on binding kinetics, affinity, specificity, thermodynamics, and concentration provided by Biacore reveals deeper biological properties of biomolecules. Applications include research, drug development and production, quality control, and biotechnology industries. As a powerful means of discovery and confirmation, accelerate the process of transforming scientific research results into biomarkers with medical value. Using Biacore technology to elucidate multiple research ideas that control cell cycle, gene transcription, cell division, and apoptotic signaling pathways will lead tumor researchers to design antagonists that can precisely inhibit key molecules in these pathways, develop and optimize for cancer diagnosis and Targeted therapeutic specific antibodies, etc., make Biacore technology not only limited to a means of verification, but also help researchers in the process of biomarker screening, increase our understanding of the specific molecular structure in the signaling pathway and Functional opportunities to further gain new treatments.
In general, with the continuous development of science and technology, the screening and production speed of biomarkers has been greatly improved. As the research progresses, researchers recognize how to validate potential biomarkers is an important prerequisite for the ultimate conversion of drug targets into clinically valuable drug targets, using accurate, rapid, and effective confirmation methods to achieve this. A strong guarantee of purpose. We believe that with the advancement of screening technology and the advancement of corroboration technology, higher quality biomarkers will be obtained, which will make biomarkers move from screening and confirmation to clinical applications.
references
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