Detection of circulating tumor DNA in patients of operative colorectal and gastric cancers.

Takeyuki Suzuki,Tetsutaro Suzuki,Jae-Hyun Park,Tetsuya Nakamura,Mitsunori Yahata,Poh Yin Yew,Yukino Yoshimura,Ryota Matsuo,Yusuke Nakamura

doi:10.18632/oncotarget.27682

Takeyuki Suzuki, Tetsutaro Suzuki + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.27682

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Journal: Oncotarget	Publication Date: Aug 25, 2020
Citations: 13	License type: cc-by

Affiliation: Japanese Foundation For Cancer Research

Abstract

Liquid biopsy is a non-invasive tool to examine the genetic profile of tumors by identification of mutated circulating tumor DNA (ctDNA), which is often analyzed by next generation sequencing (NGS) or droplet digital PCR (ddPCR) assay. We first examined the ctDNA mutation in pre-operative plasma samples obtained from 154 colorectal cancer (CRC) and 46 gastric cancer (GC) patients, using the NGS-based panel assay. The overall detection rate of mutated ctDNA was 72.0% (144 of 200 patients), and the panel-based screening identified 207 and 47 mutations from CRC and GC patients, respectively. The ddPCR analysis was then performed on post-operative samples of 77 patients, and detection of mutated ctDNA was earlier than imaging-based diagnosis in all of 6 patients who showed the tumor recurrences after surgery. Our data also revealed that patients with positive post-operation ctDNA level showed significant shorter recurrence-free survival compared to the patients with negative ctDNA level (HR 14.9; 95% CI, 0.7–313.5; p < 0.0001). These findings suggested that screening of mutated ctDNA by liquid biopsy aids in identifying the patients at high risk of post-operative recurrence, and serial screening of ctDNA would allow to monitor the response after treatment and/or early detection of tumor recurrence.

Highlights

Liquid biopsy is an emerging approach for the precision oncology, through applications in the detection of cancer cells noninvasively and repeatedly at multiple time points [1]
We examined mutation in circulating tumor DNA (ctDNA) using a panel assay for 52 cancer-related genes, and each of 144 patients showed at least 1 mutation in the ctDNA
By using 34 droplet digital PCR probes validated by our own criteria, 89 patients were available for the ddPCR-based detection of ctDNA mutation

Summary

Introduction

Liquid biopsy is an emerging approach for the precision oncology, through applications in the detection of cancer cells noninvasively and repeatedly at multiple time points [1]. The cancer-related mutations can be examined even when the tissue biopsy samples are not readily available; likely brain tumors and deeply located solid tumors. It can minimize the sampling bias caused by multiple tumor lesions or the tumor heterogeneity [2]. Based on these features, liquid biopsy can be utilized for cancer diagnosis, guidance for the matched therapies, monitoring of therapeutic response, and early detection or prediction of tumor recurrence [2,3,4,5]. The detection of mutated ctDNA could serve as a potential biomarker of www.oncotarget.com post-treatment minimal residual disease (MRD) for solid tumors including colorectal, lung, breast, and pancreatic cancer [4, 6,7,8,9]

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Conclusion