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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  

Abstract:


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)

Affiliation:

Department of Colorectal Surgery, Chinese Academy of Medical Sciences, Peking Union Medical College , Department of Pathology, Xuzhou Medical University , Geneis Beijing Co., Ltd., Geneis Beijing Co., Ltd. , Geneis Beijing Co., Ltd., Geneis Beijing Co., Ltd. , Geneis Beijing Co., Ltd., Geneis Beijing Co., Ltd. , Department of Colorectal Surgery, Chinese Academy of Medical Sciences, Peking Union Medical College, Department of Pathology, Chinese Academy of Medical Sciences and Peking Union Medical College, Geneis Beijing Co., Ltd., Department of Colorectal Surgery, Chinese Academy of Medical Sciences, Peking Union Medical College, Geneis Beijing Co., Ltd., Geneis Beijing Co., Ltd.



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