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Current Bioinformatics


ISSN (Print): 1574-8936
ISSN (Online): 2212-392X

Research Article

A Novel Method for Microsatellite Instability Detection by Liquid Biopsy Based on Next-generation Sequencing

Author(s): Zheng Jiang, Hui Liu , Siwen Zhang , Jia Liu , Weitao Wang, Guoliang Zang, Bo Meng , Huixin Lin, Jichuan Quan , Shuangmei Zou , Dawei Yuan*, Xishan Wang*, Geng Tian* and Jidong Lang*

Volume 16, Issue 1, 2021

Published on: 24 March, 2020

Page: [53 - 62] Pages: 10

DOI: 10.2174/1574893615666200324133451

Price: $65


Background: Microsatellite instability (MSI) is a prognostic biomarker used to guide medication selection in multiple cancers, such as colorectal cancer. Traditional PCR with capillary electrophoresis and next-generation sequencing using paired tumor tissue and leukocyte samples are the main approaches for MSI detection due to their high sensitivity and specificity. Currently, patient tissue samples are obtained through puncture or surgery, which causes injury and risk of concurrent disease, further illustrating the need for MSI detection by liquid biopsy.

Methods: We propose an analytic method using paired plasma/leukocyte samples and MSI detection using next-generation sequencing technology. Based on the theoretical progress of oncogenesis, we hypothesized that the microsatellite site length in plasma equals the combination of the distribution of tumor tissue and leukocytes. Thus, we defined a window-judgement method to identify whether biomarkers were stable.

Results: Compared to traditional PCR as the standard, we evaluated three methods in 20 samples (MSI-H:3/MSS:17): peak shifting method using tissue vs. leukocytes, peak shifting method using plasma vs. leukocytes, and our method using plasma vs. leukocytes. Compared to traditional PCR, we observed a sensitivity of 100%, 0%, and 100%, and a specificity of 100.00%, 94.12%, and 88.24%, respectively.

Conclusion: Our method has the advantage of possibly detecting MSI in a liquid biopsy and provides a novel direction for future studies to increase the specificity of the method.

Keywords: Microsatellite Instability (MSI), Next Generation Sequencing (NGS), Liquid Biopsy, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), biomarker.

Graphical Abstract
Boland CR, Thibodeau SN, Hamilton SR, et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 1998; 58(22): 5248-57.
[PMID: 9823339]
Thibodeau SN, Bren G, Schaid D. Microsatellite instability in cancer of the proximal colon. Science 1993; 260(5109): 816-9.
[] [PMID: 8484122]
Aaltonen LA, Peltomäki P, Leach FS, et al. Clues to the pathogenesis of familial colorectal cancer. Science 1993; 260(5109): 812-6.
[] [PMID: 8484121]
Ionov Y, Peinado MA, Malkhosyan S, Shibata D, Perucho M. Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature 1993; 363(6429): 558-61.
[] [PMID: 8505985]
Gu MJ, Huang QC, Bao CZ, et al. Attributable causes of colorectal cancer in China. BMC Cancer 2018; 18(1): 38.
[] [PMID: 29304763]
Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017; 66(4): 683-91.
[] [PMID: 26818619]
Moghimi-Dehkordi B, Safaee A. An overview of colorectal cancer survival rates and prognosis in Asia. World J Gastrointest Oncol 2012; 4(4): 71-5.
[] [PMID: 22532879]
Zarour LR, Anand S, Billingsley KG, et al. Colorectal cancer liver metastasis: evolving paradigms and future directions. Cell Mol Gastroenterol Hepatol 2017; 3(2): 163-73.
[] [PMID: 28275683]
Ryuk JP, Choi GS, Park JS, et al. Predictive factors and the prognosis of recurrence of colorectal cancer within 2 years after curative resection. Ann Surg Treat Res 2014; 86(3): 143-51.
[] [PMID: 24761423]
Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature 1998; 396(6712): 643-9.
[] [PMID: 9872311]
Boland CR, Goel A. Microsatellite instability in colorectal cancer. Gastroenterology 2010; 138(6): 2073-87.e3.
[] [PMID: 20420947]
Müller A, Edmonston TB, Dietmaier W, Büttner R, Fishel R, Rüschoff J. MSI-testing in hereditary non-polyposis colorectal carcinoma (HNPCC). Dis Markers 2004; 20(4-5): 225-36.
[] [PMID: 15528788]
Kurzawski G, Suchy J, Debniak T, Kładny J, Lubiński J. Importance of microsatellite instability (MSI) in colorectal cancer: MSI as a diagnostic tool. Ann Oncol 2004; 15(Suppl. 4): iv283-4.
[] [PMID: 15477322]
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: Colon Cancer 2018.
Hause RJ, Pritchard CC, Shendure J, Salipante SJ. Classification and characterization of microsatellite instability across 18 cancer types. Nat Med 2016; 22(11): 1342-50.
[] [PMID: 27694933]
Le DT, Uram JN, Wang H, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 2015; 372(26): 2509-20.
[] [PMID: 26028255]
Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer 2016; 16(5): 275-87.
[] [PMID: 27079802]
United States Food and Drug Administration. FDA grants accelerated approval to ipilimumab for MSI-H or dMMR metastatic colorectal cancer
United States Food and Drug Administration. FDA grants accelerated approval to ipilimumab for MSI-H or dMMR metastatic colorectal cancer
Gan C, Love C, Beshay V, et al. Applicability of next generation sequencing technology in microsatellite instability testing. Genes (Basel) 2015; 6(1): 46-59.
[] [PMID: 25685876]
Salipante SJ, Scroggins SM, Hampel HL, Turner EH, Pritchard CC. Microsatellite instability detection by next generation sequencing. Clin Chem 2014; 60(9): 1192-9.
[] [PMID: 24987110]
Niu B, Ye K, Zhang Q, et al. MSIsensor: microsatellite instability detection using paired tumor-normal sequence data. Bioinformatics 2014; 30(7): 1015-6.
[] [PMID: 24371154]
Kather JN, Pearson AT, Halama N, et al. Deep learning can predict microsatellite instability directly from histology in gastrointestinal cancer. Nat Med 2019; 25(7): 1054-6.
[] [PMID: 31160815]
Lu JL, Liang ZY. Circulating free DNA in the era of precision oncology: Pre- and post-analytical concerns. Chronic Dis Transl Med 2016; 2(4): 223-30.
[] [PMID: 29063046]
A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria 2017.
Thibodeau SN, French AJ, Cunningham JM, et al. Microsatellite instability in colorectal cancer: different mutator phenotypes and the principal involvement of hMLH1. Cancer Res 1998; 58(8): 1713-8.
[PMID: 9563488]
Gafà R, Maestri I, Matteuzzi M, et al. Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability. Cancer 2000; 89(10): 2025-37.
[<2025::AIDCNCR1>3.0.CO;2-S] [PMID: 11066042]
Mori Y, Selaru FM, Sato F, et al. The impact of microsatellite instability on the molecular phenotype of colorectal tumors. Cancer Res 2003; 63(15): 4577-82.
[PMID: 12907634]
Robertson EG, Baxter G. Tumour seeding following percutaneous needle biopsy: the real story. Clin Radiol 2011; 66(11): 1007-14.
[] [PMID: 21784421]
Crowley E, Di Nicolantonio F, Loupakis F, Bardelli A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat Rev Clin Oncol 2013; 10(8): 472-84.
[] [PMID: 23836314]

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