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    Home > Active Ingredient News > Digestive System Information > Professor Li Zhi | A meta-analysis of 5930 cases of colorectal cancer: In the Chinese population, 2B3D is more than single nucleotide detected in nearly 30% of MSI-H patients

    Professor Li Zhi | A meta-analysis of 5930 cases of colorectal cancer: In the Chinese population, 2B3D is more than single nucleotide detected in nearly 30% of MSI-H patients

    • Last Update: 2021-03-23
    • Source: Internet
    • Author: User
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    【Introduction】Professor Li Zhi, Director of the Department of Pathology, Guangdong Provincial People's Hospital, led a meta-analysis of the positive detection rate data of Panels at different MSI detection sites in the Chinese population.
    The results and data have been published in the Journal of Gastrointestinal Oncology .

    Microsatellite instability (MSI) is a very important pan-cancer marker, and its test results have multi-dimensional clinical detection significance in multiple cancers.
    The domestic and foreign guideline consensus recommends all colorectal cancer, gastric cancer, and endometrial cancer.
    Cancer, small bowel adenocarcinoma, and pancreatic cancer patients undergo MSI testing.

    In addition, patients with Lynch syndrome-related cancers and patients with solid tumors who have the opportunity to receive immunotherapy are also recommended for MSI testing.

    Therefore, MSI should be fully checked is the detection strategy that the above-mentioned tumor patients need to refer to.

    The PCR + capillary electrophoresis method is regarded as the gold standard of MSI detection due to its stable method and high detection sensitivity [1].
    The site selection in this method is extremely important and is closely related to the subsequent diagnosis and treatment decisions of patients.It is reported that there are 19 million microsatellite sites in the human genome, and defects in the mismatch repair system will not cause all microsatellite sites to be unstable.
    So which sites should we detect? At present, there are mainly two sets of detection sites recommended by domestic and foreign guidelines.
    One set is the 2B3D NCI Panel (BAT-25, BAT-26, D5S346, D17S250, D2S123) proposed in the NCI (Bethesda) guidelines issued in 1997.
    Studies have found that the sensitivity of single nucleotides may be higher than that of double nucleotides.
    Therefore, it was proposed in the Revised Bethesda guide in 2004 that in addition to 2B3D, a Pentaplex Panel consisting of 5 single nucleotide microsatellite sites can also be used.
    (BAT-25, BAT-26, NR-21, NR-22, NR-24), later due to the modification of the Pentaplex Panel by American Promega Company and the production of commercial kits for MSI detection (BAT-25, BAT -26, NR-21, NR-24, MONO-27), so the application of this kit abroad is more extensive than the original Pentaplex Panel.

    In addition, large-scale international clinical studies mainly use 2B3D NCI Panel and Promega Panel to assess the status of MSI.

    However, microsatellites are actually well-known STR sites and are often used in forensic identification.
    Microsatellites are different in different races, such as the incidence of MSI-H in African American colorectal cancer (about 45%).
    ) Is much higher than the Chinese population (about 15%).

    The above-mentioned comparisons of single nucleotide and double nucleotide sensitivity are based on data from European and American populations.
    In European and American populations, single nucleotide sensitivity may be higher, but is it consistent with European and American populations in Chinese population? In order to answer this question, Professor Li Zhi, Director of the Department of Pathology, Guangdong Provincial People’s Hospital, led a meta-analysis of the positive detection rate data of Panels at different MSI detection sites in the Chinese population.
    The results and data have been published in the Journal of Gastrointestinal Published in Oncology journal.In order to explore the positive detection rate of different MSI panels in the Chinese population, the research team conducted a review of PubMed, Embase, Web of Science, CNKI, Wanfang, CQVIP, and China Biomedical Literature Database.
    (CBM) and other databases were searched to obtain studies based on the use of PCR+capillary electrophoresis in the Chinese population to detect the MSI status of sporadic colorectal cancer since 2000, and the literature screening was completed through specific criteria, and finally 17 studies were included in the analysis.

    All studies included in the analysis were evaluated by the Newcastle-Ottawa Scale (NOS) Literature Quality Evaluation Scale.

    Then, the research data was extracted into groups, and the MSI-H detection rate of different panels in the Chinese population was meta-analyzed, so as to compare the detection rate data of each Panel to identify the sites with the highest detection rate in the Chinese population.
    The combination provides a data reference for the selection of MSI detection sites in the Chinese population.

    According to the 17 studies, detection sites mainly include two categories: the first category is 2B3D NCI Panel containing dinucleotides, and the other category is single nucleotide sites.

    Among them, 10 studies used the "2B3D NCI Panel" with a total of 2681 samples; another 4 studies used the Promega Panel with a total of 640 samples; another 3 studies used 6 single nucleotide sites (BAT25, BAT26, NR-21, NR-24, MONO-27, NR-27), a total of 2609 samples.

     Figure 1 The information of the enrolled study was analyzed by meta-analysis of the detection rates of all subgroups.
    The results showed that the detection rate of MSI-H in the 2B3D NCI Panel was higher than that of single nucleotides, reaching 13.
    5% (95%CI: 10.
    8-16.
    4) ; The detection rate of the overall single nucleotide subgroup was 10.
    6% (95%CI: 7.
    1-14.
    7), of which the detection rate of the Promega subgroup was 12.
    9% (95%CI: 8.
    3-18.
    3), slightly lower than 2B3D In the subgroup, the detection rate of the 6 single-nucleotide site subgroup was low, being 7.
    7% (95%CI: 4.
    7-11.
    2). In comparison, the 2B3D subgroup has a 27.
    4% higher detection rate than the single nucleotide subgroup, and a 54.
    7% higher detection rate than the 6 single nucleotide subgroup.

    Fig.
    2 Forest diagram of the detection rate of MSI-H tumors in 2B3D NCI Panel subgroupsFig.
    3 Forest diagram of the detection rate of MSI-H tumors in single nucleotide subgroupsFig.
    4 Detection rates of MSI-H tumors in 6 single nucleotide subgroups The results of the forest map study suggest that in the Chinese population, the 2B3D NCI Panel detects nearly 30% more MSI-H patients than the single nucleotide Panel.

    The article mentioned that in the early twentieth century, the Revised Bethesda guide mentioned that the sensitivity of the single-nucleotide site detection Panel was higher than that of the 2B3D NCI Panel containing binucleotide sites [2].
    Therefore, the conclusions and guidelines of this study Contradictory.

    One of the underlying reasons is that the early studies are from European and American populations, and the incidence of instability of microsatellite sites is ethnically different [3].

    Previous multi-center studies have compared the detection sensitivity of 2B3D NCI Panel with 5 single nucleotide sites in the Chinese population, and the results consistently show that the detection sensitivity of 2B3D NCI Panel in the Chinese population is higher than 5 single nucleotide sites.
    Location [4, 5], this meta-analysis also confirmed this conclusion again, that is to say, the results of the research data in the Chinese population are exactly the opposite of the European and American populations.

    It can be seen that the site selection of MSI detection is very critical in different populations.

    In addition to ethnic differences, there may be other reasons.

    We know that the defects of MMR will not cause all microsatellites to be unstable, and the instability incidence of each microsatellite is different, so the detection rate of different site combinations will be different.

    Moreover, there may be differences between sporadic and genetically unstable sites.
    Studies have shown that the sensitivity of single nucleotide sites in Lynch syndrome patients may be higher than that of dinucleotides[2] As we all know, in the past, MSI testing was mainly used for Lynch syndrome screening, so this may also be the reason why Revised Bethesda proposed higher single-nucleotide sensitivity. However, the detection of MSI is now more to guide immunotherapy, and more patients with sporadic MSI-H tumors can benefit from immunotherapy, so dinucleotide may have a higher incidence of instability in sporadic tumors.
    So this is also a new direction that MSI is worth exploring.

    In summary, the Chinese population uses 2B3D NCI Panel to detect nearly 30% more MSI-H tumors than the single nucleotide Panel.
    Therefore, the widespread use of 2B3D NCI Panel in the Chinese population can avoid the missed detection of MSI-H tumors.
    More optimal site selection maximizes the benefits of true MSI-H tumor patients. Expert introduction: Professor Li Zhi, Chief Physician, Director of the Department of Pathology, Guangdong Provincial People's Hospital, Deputy Leader of the Head and Neck Pathology Group, Chinese Medical Association Pathology Branch, Member of the Neuropathology Group, Chinese Medical Association Pathology Branch, National Committee of the Chinese Medical Association Pathologists Branch, China Anti-Cancer National Committee of the Association's Cancer Pathology Committee, Chairman of the Pathology Committee of the Guangdong Primary Medicine Society, Deputy Chairman of the Guangdong Pathologists Branch, Deputy Chairman of the Guangdong Pathology Branch of the Chinese and Western Medicine Association Deputy Chairman of the Guangdong Neuro-Oncology Professional Committee of the Chinese Anti-Cancer Association Chairman, Director of Neuropathology Group of Guangdong Pathologists Association of Chinese Medical Doctor Association, editorial board member of Chinese journals such as Chinese Journal of Pathology, and reference for reviewers of SCI-included journals such as "Neuropathology" and "PLOS ONE" and domestic core journals Literature 1.
    Baudrin, LG, JF Deleuze, and A.
    How-Kit, Molecular and Computational Methods for the Detection of Microsatellite Instability in Cancer.
    Front Oncol, 2018.
    8: p.
    621.
    2.
    Umar, A.
    , et al.
    , Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability.
    J Natl Cancer Inst, 2004.
    96(4): p.
    261-268.
    3.
    Vilar, E.
    and SB Gruber, Microsatellite instability in colorectal cancer-the stable evidence.
    Nat Rev Clin Oncol, 2010.
    7(3): p.
    153-162.
    4.
    Bai, W.
    , et al.
    ,Screening of MSI detection loci and their heterogeneity in East Asian colorectal cancer patients.
    Cancer Med, 2019.
    8(5): p.
    2157-2166.
    5.
    Zheng, J.
    , et al.
    , The clinicopathological features and prognosis of tumor MSI in East Asian colorectal cancer patients using NCI panel.
    Future Oncol, 2018.
    14(14): p.
    1355-1364.
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