Non‐Invasive Tumor‐Naïve Minimal Residual Disease Detection of Liver Cancer by Incorporating Circulating Tumor DNA Features and Alpha‐Fetoprotein: A Prospective Study

ABSTRACT Background and Purpose Liver cancer has a high recurrence rate of 50%~70% for early‐stage patients. Minimal residual disease (MRD) is strongly linked to liver cancer early recurrence. Identifying MRD through reliable prognostic biomarkers, such as circulating tumor DNA (ctDNA), could signif...

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Main Authors: Qingqi Ren, Shiyong Li, Guolin Zhong, Yunfei Li, Dao‐Ling Huang, Liangliang Zhang, Yumin Feng, Guanghui Long, Mao Mao
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.70511
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author Qingqi Ren
Shiyong Li
Guolin Zhong
Yunfei Li
Dao‐Ling Huang
Liangliang Zhang
Yumin Feng
Guanghui Long
Mao Mao
author_facet Qingqi Ren
Shiyong Li
Guolin Zhong
Yunfei Li
Dao‐Ling Huang
Liangliang Zhang
Yumin Feng
Guanghui Long
Mao Mao
author_sort Qingqi Ren
collection DOAJ
description ABSTRACT Background and Purpose Liver cancer has a high recurrence rate of 50%~70% for early‐stage patients. Minimal residual disease (MRD) is strongly linked to liver cancer early recurrence. Identifying MRD through reliable prognostic biomarkers, such as circulating tumor DNA (ctDNA), could significantly benefit these patients by enabling timely intervention and improved outcomes. Materials and Methods A prospective study enrolled 32 liver cancer patients undergoing radical surgery. Peripheral blood samples (8 mL) were collected before and after surgery. In this study, we expanded upon our previously developed multi‐omics assay, initially designed for liver cancer early detection by calculating a cancer signal score (PHCC), to determine the MRD status (named SeekInCure). This process integrated protein tumor marker alpha‐fetoprotein (AFP) and cancer genomic hallmarks, copy number aberration (CNA) and fragment size (FS). Results Of the enrolled patients, 78.1% were in early stages, and before surgery, 87.5% of patients had successfully detected the cancer signal in blood. After radical surgery, 23 patients were MRD‐negative, exhibiting better overall survival compared to the MRD‐positive patients (n = 9, p < 0.01). Patients maintaining undetectable cancer signals pre‐ and post‐surgery showed 100% survival, conversely, those keeping with detectable signals had a 55.6% mortality rate. Conclusion This prospective study highlights the prognostic value of ctDNA‐based tumor‐naïve MRD detection through a multi‐omics assay in early‐stage liver cancer patients.
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spelling doaj-art-240c162b8e754f1b8f0327ab3910103a2025-01-20T10:51:32ZengWileyCancer Medicine2045-76342024-12-011324n/an/a10.1002/cam4.70511Non‐Invasive Tumor‐Naïve Minimal Residual Disease Detection of Liver Cancer by Incorporating Circulating Tumor DNA Features and Alpha‐Fetoprotein: A Prospective StudyQingqi Ren0Shiyong Li1Guolin Zhong2Yunfei Li3Dao‐Ling Huang4Liangliang Zhang5Yumin Feng6Guanghui Long7Mao Mao8Department of Hepatopancreatobiliary Surgery Peking University Shenzhen Hospital Shenzhen ChinaResearch & Development, SeekIn Inc. Shenzhen ChinaResearch & Development, SeekIn Inc. Shenzhen ChinaResearch & Development, SeekIn Inc. Shenzhen ChinaResearch & Development, SeekIn Inc. Shenzhen ChinaClinical Laboratories Shenyou Bio Zhengzhou ChinaResearch & Development, SeekIn Inc. Shenzhen ChinaDepartment of Hepatopancreatobiliary Surgery Peking University Shenzhen Hospital Shenzhen ChinaResearch & Development, SeekIn Inc. San Diego California USAABSTRACT Background and Purpose Liver cancer has a high recurrence rate of 50%~70% for early‐stage patients. Minimal residual disease (MRD) is strongly linked to liver cancer early recurrence. Identifying MRD through reliable prognostic biomarkers, such as circulating tumor DNA (ctDNA), could significantly benefit these patients by enabling timely intervention and improved outcomes. Materials and Methods A prospective study enrolled 32 liver cancer patients undergoing radical surgery. Peripheral blood samples (8 mL) were collected before and after surgery. In this study, we expanded upon our previously developed multi‐omics assay, initially designed for liver cancer early detection by calculating a cancer signal score (PHCC), to determine the MRD status (named SeekInCure). This process integrated protein tumor marker alpha‐fetoprotein (AFP) and cancer genomic hallmarks, copy number aberration (CNA) and fragment size (FS). Results Of the enrolled patients, 78.1% were in early stages, and before surgery, 87.5% of patients had successfully detected the cancer signal in blood. After radical surgery, 23 patients were MRD‐negative, exhibiting better overall survival compared to the MRD‐positive patients (n = 9, p < 0.01). Patients maintaining undetectable cancer signals pre‐ and post‐surgery showed 100% survival, conversely, those keeping with detectable signals had a 55.6% mortality rate. Conclusion This prospective study highlights the prognostic value of ctDNA‐based tumor‐naïve MRD detection through a multi‐omics assay in early‐stage liver cancer patients.https://doi.org/10.1002/cam4.70511AFPCNAfragment sizeliver cancerMRDsWGS
spellingShingle Qingqi Ren
Shiyong Li
Guolin Zhong
Yunfei Li
Dao‐Ling Huang
Liangliang Zhang
Yumin Feng
Guanghui Long
Mao Mao
Non‐Invasive Tumor‐Naïve Minimal Residual Disease Detection of Liver Cancer by Incorporating Circulating Tumor DNA Features and Alpha‐Fetoprotein: A Prospective Study
Cancer Medicine
AFP
CNA
fragment size
liver cancer
MRD
sWGS
title Non‐Invasive Tumor‐Naïve Minimal Residual Disease Detection of Liver Cancer by Incorporating Circulating Tumor DNA Features and Alpha‐Fetoprotein: A Prospective Study
title_full Non‐Invasive Tumor‐Naïve Minimal Residual Disease Detection of Liver Cancer by Incorporating Circulating Tumor DNA Features and Alpha‐Fetoprotein: A Prospective Study
title_fullStr Non‐Invasive Tumor‐Naïve Minimal Residual Disease Detection of Liver Cancer by Incorporating Circulating Tumor DNA Features and Alpha‐Fetoprotein: A Prospective Study
title_full_unstemmed Non‐Invasive Tumor‐Naïve Minimal Residual Disease Detection of Liver Cancer by Incorporating Circulating Tumor DNA Features and Alpha‐Fetoprotein: A Prospective Study
title_short Non‐Invasive Tumor‐Naïve Minimal Residual Disease Detection of Liver Cancer by Incorporating Circulating Tumor DNA Features and Alpha‐Fetoprotein: A Prospective Study
title_sort non invasive tumor naive minimal residual disease detection of liver cancer by incorporating circulating tumor dna features and alpha fetoprotein a prospective study
topic AFP
CNA
fragment size
liver cancer
MRD
sWGS
url https://doi.org/10.1002/cam4.70511
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