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

Development a Pulmonary Nodules Diagnosis Classification Model for Benign/Malignant of Bronchoscopic Biopsy Specimens Based on High-throughput Whole-genome Methylation Sequencing(GM-seq)

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Nodule, Solitary; Whole-genome Methylation Sequencing
• Intervention / Treatment: Diagnostic test: Whole-genome Methylation Sequencing(GM-seq)

• Study Type: Observational
• Enrollment (Actual): 158

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100730
      • Beijing Hospital
    • Beijing, Beijing Municipality, China, 100028
      • Emergency General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Subjects with pulmonary nodules suspected of early lung cancer

Description

Inclusion Criteria:

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

Exclusion criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
[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); 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.
[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); 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Geneplus-Beijing Co. Ltd.
• Collaborators: Beijing Hospital; Emergency General Hospital
• Investigators: Study Chair: Wei Zhou, Doctor, Beijing Hospital; Study Director: Yunzhi Zhou, Doctor, Emergency General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Actual): June 1, 2025
• Study Completion (Actual): August 1, 2025

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 8, 2022
• First Posted (Actual): June 13, 2022

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: August 27, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: ctDNA; Machine learning; Pulmonary Nodule, Solitary; Whole-genome Methylation Sequencing(GM-seq)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Solitary Pulmonary Nodule
• Other Study ID Numbers: GM-Lung diagnosis

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No