Benign/Malignant Pulmonary Nodule Classification Based on High-throughput Whole-genome Methylation Sequencing(GM-seq)

NCT05415670 | Completed

• 1 other identifier: GM-Lung diagnosis
• Study Type: observational
• Target: 158
• Locations: 1 country
• Sites: 2

Brief Summary

Lung cancer is the first cancer in China in terms of morbidity and mortality. The problem of early diagnosis/treatment has always been concerned. The popularization of chest CT (electronic computed tomography) screening makes it possible to detect lung cancer early. However, the diagnosis still needs pathological evidence. It is an ideal choice to obtain pathological evidence through bronchoscope and other minimally invasive means before surgical resection. However, the positive rate of tracheoscopy is still unsatisfactory, which is related to the difficulty of traditional pathological detection in detecting small specimens obtained by tracheoscopy. Liquid biopsy technology based on methylation detection has been used in early cancer screening, but its advantages have not been fully exploited due to the low content of ctDNA (circulating tumor DNA) in the current detection samples. Therefore, through prospective clinical research, the investigators plan to combine the methylation detection technology based on "Whole genome methylation sequencing(GM-seq)" with tracheoscopy, compare the traditional pathological methods with methylation detection on the bronchoscopic samples of lung nodule subjects suspected of early lung cancer, and take the postoperative pathology as the gold standard for judging benign and malignant, to confirm the feasibility and advantages of the new technology.

Conditions

Pulmonary Nodule, Solitary; Whole-genome Methylation Sequencing

Keywords

ctDNA; Pulmonary Nodule, Solitary; Whole-genome Methylation Sequencing(GM-seq); Machine learning

Outcome Measures

Primary Outcomes (1)

• Area under the receiver operating characteristic curve (ROC)

  Area under curve (AUC) of GM-seq data in discriminating malignant nodules from benign nodules.

  2 years

Study Arms (2)

[Training set, N=80] Benign/Malignant Pulmonary Nodule

This is a prospective training-set cohort study. A stratified case-cohort design will be used to select patients with malignant pulmonary nodules and patients with benign pulmonary nodules for analysis. All participants will receive chest CT or low-dose computed tomography (LD-CT) scanning and detection of serum tumor markers, and receive Whole-genome methylation sequencing at baseline. GM-seq will perform methylation analysis to build a prediction model for benign and malignant classification.

Diagnostic Test: Whole-genome Methylation Sequencing(GM-seq)

[Verification set, N=40] Benign/Malignant Pulmonary Nodule

This is a prospective validation-set cohort study. A stratified case-cohort design was used to select patients with malignant pulmonary nodules and patients with benign pulmonary nodules for analysis. All participants will verify the benign and malignant differentiation model based on GM-seq methylation analysis, and compare the results with histopathological benign and malignant results, so as to develop a clinical benign and malignant differentiation model.

Diagnostic Test: Whole-genome Methylation Sequencing(GM-seq)

Interventions

Whole-genome Methylation Sequencing(GM-seq) DIAGNOSTIC_TEST

A Whole-genome Methylation detection method, which can analyze the genome-wide, single base resolution methylation of tissue / blood samples, and is used to develop a benign and malignant classification model for Pulmonary Nodule.

[Training set, N=80] Benign/Malignant Pulmonary Nodule; [Verification set, N=40] Benign/Malignant Pulmonary Nodule

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Subjects with pulmonary nodules suspected of early lung cancer

You may qualify if:

• Male or female, 20-75 year-old with pulmonary nodules 1-3cm in diameter confirmed by chest CT;
• The nodules are single or multiple, suspected to be malignant, and have the indication of surgical resection;
• Patient accept imaging evaluation without advanced lung tumors and metastases;
• The location of the nodule in the lung is within the reach of lung biopsy under bronchoscope;
• provide the collected clinical data needed by the research;
• Patients have the ability to follow the planned schedule and actively cooperate to return to the hospital for regular clinical visits.

You may not qualify if:

• Unwilling to accept the invasive examination and treatment of this study;
• Contraindication of tracheoscopy;
• Consider that the pulmonary nodules are metastatic tumors or unresectable advanced lung cancer;
• Those who cannot tolerate resection of pulmonary nodules;
• Accompanied by other malignant tumors;
• In the judgment of the researcher, the patient also suffers from other serious diseases that may affect the accuracy of the test;
• Those who cannot accept the use of contrast-enhanced magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT);
• Any other illness, social / psychological problems, etc. are judged by the researcher to be unsuitable for participating in this study.

Sponsors & Collaborators

• Geneplus-Beijing Co. Ltd.: lead
• Beijing Hospital: collaborator
• Emergency General Hospital: collaborator

Study Sites (2)

Emergency general hospital

Beijing, Beijing Municipality, 100028, China

Location

Beijing hospital

Beijing, Beijing Municipality, 100730, China

Location

MeSH Terms

Conditions

Solitary Pulmonary Nodule

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Study Officials

• Wei Zhou, Doctor

  Beijing Hospital

  STUDY CHAIR

• Yunzhi Zhou, Doctor

  Emergency General Hospital

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: June 13, 2022
• Study Start: July 1, 2023
• Primary Completion: June 1, 2025
• Study Completion: August 1, 2025
• Last Updated: September 4, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)