Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor‐informed assay
Abstract Background Circulating tumor DNA (ctDNA)‐based minimal residual disease (MRD) detection, which can identify disease relapse ahead of radiological imaging, has shown promising performance. The objective of this study was to develop and validate OriMIRACLE S (Minimal Residual Circulating Nucl...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-08-01
|
| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.6286 |
| _version_ | 1797242676077133824 |
|---|---|
| author | Zining Qi Yi Li ZhengKun Wang Xuerong Tan Yixuan Zhou Zhendong Li Weirong Zhao Xin Zheng Jicheng Yao Feng Li Weifeng Wang Zhizheng Wang Fei Pang Gang Wang Weiguang Gu |
| author_facet | Zining Qi Yi Li ZhengKun Wang Xuerong Tan Yixuan Zhou Zhendong Li Weirong Zhao Xin Zheng Jicheng Yao Feng Li Weifeng Wang Zhizheng Wang Fei Pang Gang Wang Weiguang Gu |
| author_sort | Zining Qi |
| collection | DOAJ |
| description | Abstract Background Circulating tumor DNA (ctDNA)‐based minimal residual disease (MRD) detection, which can identify disease relapse ahead of radiological imaging, has shown promising performance. The objective of this study was to develop and validate OriMIRACLE S (Minimal Residual Circulating Nucleic Acid Longitudinal Detection in Solid Tumor), a highly sensitive and specific tumor‐informed assay for MRD detection. Methods Tumor‐specific somatic single nucleotide variants (SNVs) were identified via whole exome sequencing of tumor tissue and matched germline DNA. Clonal SNVs were selected using the OriSelector algorithm for patient‐specific, multiplex PCR‐based NGS assays in MRD detection. Plasma‐free DNA from patients with gastrointestinal tumors prior to and following an operation, and during monitoring, were ultradeep sequenced. Results The detection of three positive sites was sufficient to achieve nearly 100% overall sample level sensitivity and specificity and was determined by calculating binomial probability based on customized panels containing 21 to 30 variants. A total of 127 patients with gastrointestinal tumors were enrolled in our study. Preoperatively, MRD was positive in 18 of 26 patients (69.23%). Following surgery, MRD was positive in 24 of 82 patients (29.27%). The positivity rate for MRD was 33.33% (n = 18) for gastric adenocarcinoma and 32.26% (n = 62) for colorectal cancer. Twenty (20) of 59 patients (34.48%) experienced a change in MRD status over the monitoring period. Patients 8 and 31 responded to 3 cycles of systemic therapy, after which levels for all ctDNA dropped below the detection limit. Patient 53 was an example of using MRD to predict tumor metastasis. Patient 55 showed a weak response to treatments first and respond to new systemic therapy after tumor progression. Conclusion Our study identified a sensitive and specific clinical detection method for low frequency ctDNA, and explored the detection performance of this technology in gastrointestinal tumors. |
| first_indexed | 2024-03-12T00:55:00Z |
| format | Article |
| id | doaj.art-2b3c933c044e43afbf67e5f0ffd05caf |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-24T18:43:00Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-2b3c933c044e43afbf67e5f0ffd05caf2024-03-27T09:11:00ZengWileyCancer Medicine2045-76342023-08-011216166871669610.1002/cam4.6286Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor‐informed assayZining Qi0Yi Li1ZhengKun Wang2Xuerong Tan3Yixuan Zhou4Zhendong Li5Weirong Zhao6Xin Zheng7Jicheng Yao8Feng Li9Weifeng Wang10Zhizheng Wang11Fei Pang12Gang Wang13Weiguang Gu14Department of Gastrointestinal surgery The First Hospital of Shanxi Medical University Taiyuan ChinaDepartment of Gastrointestinal surgery The Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Gastrointestinal surgery The Affiliated Hospital of Qingdao University Qingdao ChinaDepartment of Radiology The Second Hospital of Dalian Medical University Dalian ChinaDepartment of Radiology The Second Hospital of Dalian Medical University Dalian ChinaShanghai OrigiMed Co., Ltd Shanghai ChinaShanghai OrigiMed Co., Ltd Shanghai ChinaShanghai OrigiMed Co., Ltd Shanghai ChinaShanghai OrigiMed Co., Ltd Shanghai ChinaShanghai OrigiMed Co., Ltd Shanghai ChinaShanghai OrigiMed Co., Ltd Shanghai ChinaShanghai OrigiMed Co., Ltd Shanghai ChinaShanghai OrigiMed Co., Ltd Shanghai ChinaDepartment of General Surgery Jiangsu Province Hospital of Chinese Medicine Nanjing ChinaDepartment of oncology Nanhai People's Hospital Foshan ChinaAbstract Background Circulating tumor DNA (ctDNA)‐based minimal residual disease (MRD) detection, which can identify disease relapse ahead of radiological imaging, has shown promising performance. The objective of this study was to develop and validate OriMIRACLE S (Minimal Residual Circulating Nucleic Acid Longitudinal Detection in Solid Tumor), a highly sensitive and specific tumor‐informed assay for MRD detection. Methods Tumor‐specific somatic single nucleotide variants (SNVs) were identified via whole exome sequencing of tumor tissue and matched germline DNA. Clonal SNVs were selected using the OriSelector algorithm for patient‐specific, multiplex PCR‐based NGS assays in MRD detection. Plasma‐free DNA from patients with gastrointestinal tumors prior to and following an operation, and during monitoring, were ultradeep sequenced. Results The detection of three positive sites was sufficient to achieve nearly 100% overall sample level sensitivity and specificity and was determined by calculating binomial probability based on customized panels containing 21 to 30 variants. A total of 127 patients with gastrointestinal tumors were enrolled in our study. Preoperatively, MRD was positive in 18 of 26 patients (69.23%). Following surgery, MRD was positive in 24 of 82 patients (29.27%). The positivity rate for MRD was 33.33% (n = 18) for gastric adenocarcinoma and 32.26% (n = 62) for colorectal cancer. Twenty (20) of 59 patients (34.48%) experienced a change in MRD status over the monitoring period. Patients 8 and 31 responded to 3 cycles of systemic therapy, after which levels for all ctDNA dropped below the detection limit. Patient 53 was an example of using MRD to predict tumor metastasis. Patient 55 showed a weak response to treatments first and respond to new systemic therapy after tumor progression. Conclusion Our study identified a sensitive and specific clinical detection method for low frequency ctDNA, and explored the detection performance of this technology in gastrointestinal tumors.https://doi.org/10.1002/cam4.6286circulating tumor DNAgastrointestinal carcinomamolecular residual diseasetumor metastasis |
| spellingShingle | Zining Qi Yi Li ZhengKun Wang Xuerong Tan Yixuan Zhou Zhendong Li Weirong Zhao Xin Zheng Jicheng Yao Feng Li Weifeng Wang Zhizheng Wang Fei Pang Gang Wang Weiguang Gu Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor‐informed assay Cancer Medicine circulating tumor DNA gastrointestinal carcinoma molecular residual disease tumor metastasis |
| title | Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor‐informed assay |
| title_full | Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor‐informed assay |
| title_fullStr | Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor‐informed assay |
| title_full_unstemmed | Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor‐informed assay |
| title_short | Monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor DNA using a tumor‐informed assay |
| title_sort | monitoring of gastrointestinal carcinoma via molecular residual disease with circulating tumor dna using a tumor informed assay |
| topic | circulating tumor DNA gastrointestinal carcinoma molecular residual disease tumor metastasis |
| url | https://doi.org/10.1002/cam4.6286 |
| work_keys_str_mv | AT ziningqi monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT yili monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT zhengkunwang monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT xuerongtan monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT yixuanzhou monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT zhendongli monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT weirongzhao monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT xinzheng monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT jichengyao monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT fengli monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT weifengwang monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT zhizhengwang monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT feipang monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT gangwang monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay AT weiguanggu monitoringofgastrointestinalcarcinomaviamolecularresidualdiseasewithcirculatingtumordnausingatumorinformedassay |