Evidence map›Paper›PMID 40468355›Full record

Observational studyMolecular cancer2025

GUIDE: a prospective cohort study for blood-based early detection of gastrointestinal cancers using targeted DNA methylation and fragmentomics sequencing.

Ao Huang, De-Zhen Guo, Zhi-Xi Su, Yun-Shi Zhong, Liang Liu, Zhi-Guo Xiong, Dong-Li He, Bin Yan, Quan-Lin Li, Zhen Feng and 19 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Molecular cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05431621 (Establishment of Molecular Classification Models for Early Diagnosis of Digestive System Cancers), which is not on this map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05431621 completednot on this map

Establishment of Molecular Classification Models for Early Diagnosis of Digestive System Cancers

TypeobservationalSponsorShanghai Zhongshan HospitalRan2020 to 2023Enrolled2,430ConditionsEsophageal Cancer, Gastric (Stomach) Cancer, Colorectal Cancer, Hepatocellular Carcinoma
3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Ao Huang *Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China.
De-Zhen Guo *Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China.
Zhi-Xi Su *Singlera Genomics (Shanghai) Ltd., Shanghai, 201203, China.
Yun-Shi Zhong *Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Liang Liu *Department of Pancreatic Surgery, Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, Cancer Center, Shanghai, 200032, China.
Zhi-Guo Xiong *Department of Gastrointestinal Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, China.
Dong-Li HeDepartment of Gastroenterology, Xuhui Central Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200031, China.
Bin YanDepartment of Clinical Laboratory, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, 201700, China.
Quan-Lin LiEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Zhen FengDepartment of Gastroenterology, Xuhui Central Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200031, China.
Wen-Quan WangDepartment of Pancreatic Surgery, Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, Cancer Center, Shanghai, 200032, China.
Pin-Xiang LuDepartment of General Surgery, Xuhui Central Hospital, Shanghai, 20031, China.
Meng-Jiang HeEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Zhi-Peng QiEndoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Qi GuoEndoscopy Center, Xuhui Central Hospital, Zhongshan Hospital, Fudan University, Shanghai, 200031, China.
Jian-Wen ChengDepartment of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China.
Shi-Yu ZhangDepartment of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China.
Wei GuoDepartment of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Qing LiXiangya Medical Laboratory, Central South University, Changsha, 410078, China.
Guo-Yong LinDepartment of Respiratory and Critical Illness Medicine, The First Hospital of Putian, Putian, 351100, China.
Hui-Chuan SunDepartment of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China.
Shuang-Jian QiuDepartment of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China.
Qi-Ye HeSinglera Genomics (Shanghai) Ltd., Shanghai, 201203, China.
Jia FanDepartment of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China.
Ajay GoelDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Biomedical Research Center, Monrovia, CA, USA.
Rui LiuSinglera Genomics (Shanghai) Ltd., Shanghai, 201203, China. rliu@singleragenomics.com.
Gang JinDepartment of Hepatobiliary Pancreatic Surgery, Changhai Hospital, Navy Medical University (the Second Military Medical University), Shanghai, 200433, China. jingang@smmu.edu.cn.
Xin-Rong YangDepartment of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China. yang.xinrong@zs-hospital.sh.cn.
Jian ZhouDepartment of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai, 200032, China. zhou.jian@zs-hospital.sh.cn.

Funding

National Key Research and Development Program of China 2019YFC1315800National Key Research and Development Program of China 2019YFC1315802National Key Research and Development Program of China 2021YFC2501900National Natural Science Foundation of China 82072715National Natural Science Foundation of China 82341027National Natural Science Foundation of China 82488101Original Discovery Program of National Natural Science Foundation of China 82150004Science Foundation of Zhongshan Hospital, Fudan University 2020ZSLC31Science Foundation of Zhongshan Hospital, Fudan University 2021ZSCX28Shanghai hospital development center SHDC2023CRD025Shanghai Municipal Health Commission 201940075Shanghai Municipal Health Commission 2022LJ005Shanghai Science and Technology Commission 21140900300Shanghai Science and Technology Commission 22S31901800State Key Program of the National Natural Science Foundation of China 81830102
6 · The paper itself

Abstract

backgroundGastrointestinal (GI) cancers are among the most prevalent and lethal malignancies worldwide. Early, non-invasive detection is essential for timely intervention and improved survival. To address this clinical need, we developed GutSeer, a blood-based assay combining DNA methylation and fragmentomics for multi-GI cancer detection.

methodsGenome-wide methylome profiling identified 1,656 markers specific to five major GI cancers and their tissue origins. Based on these findings, we designed GutSeer, a targeted bisulfite sequencing panel, which was trained and validated using plasma samples from 1,057 cancer patients and 1,415 non-cancer controls. The locked model was blindly tested in an independent cohort of 846 participants, encompassing both inpatient and outpatient settings across five hospitals.

resultsIn the validation cohort, GutSeer achieved an area under the curve (AUC) of 0.950 [95% Confidence Interval (CI): 0.937-0.962] for cancer detection, with 82.8% sensitivity (95% CI: 79.5-86.0) and 95.8% specificity (95% CI: 94.3-97.2). It detected 92.2% of colorectal, 75.5% of esophageal, 65.3% of gastric, 92.9% of liver, and 88.6% of pancreatic cancers. The independent test cohort included 198 early-stage cancers (stage I/II, 66.4%) and 63 advanced precancerous lesions. GutSeer maintained robust performance, with 81.5% sensitivity (95% CI: 77.1-85.9) for GI cancers and 94.4% specificity (95% CI: 92.4-96.5). It also demonstrated the ability to detect advanced precancerous lesions in the colorectum, esophagus, and stomach as a single, non-invasive blood test.

conclusionsBy integrating DNA methylation and fragmentomics into a compact panel, GutSeer outperformed genome-wide sequencing in both accuracy and clinical applicability. Its high sensitivity for early-stage GI cancers and practicality as a non-invasive assay highlights its potential to revolutionize early cancer detection and improve patient outcomes.

trial registrationClinicalTrials.gov identifier: NCT05431621.

Indexed as

Biomarkers, TumorDNA MethylationEarly Detection of CancerGastrointestinal NeoplasmsAgedFemaleHumansMaleMiddle AgedProspective StudiesROC CurveSequence Analysis, DNABiomarkers, TumorCell-free DNA (cfDNA)FragmentomicsGastrointestinal cancerMethylationMulti-cancer early detection (MCED)Multi-dimensional features

Identifiers

PMID40468355
PMCPMC12139136

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.