Title:A Novel Method for Microsatellite Instability Detection by Liquid Biopsy Based on Next-generation Sequencing
Volume: 16
Issue: 1
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*Jidong Lang*
Affiliation:
- Geneis Beijing Co., Ltd., Beijing 100102,China
- Department of Colorectal Surgery, Cancer Institute & Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021,China
- Geneis Beijing Co., Ltd., Beijing 100102,China
- Geneis Beijing Co., Ltd., Beijing 100102,China
Keywords:
Microsatellite Instability (MSI), Next Generation Sequencing (NGS), Liquid Biopsy, cell-free DNA (cfDNA),
circulating tumor DNA (ctDNA), biomarker.
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.
