Application of Methylation Markers in Early Detection and MRD Monitoring of Lung Cancer

NCT07257458 | Recruiting

• 1 other identifier: M202535
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to evaluate the utility of combined plasma SHOX2 and PTGER4 gene methylation analysis as a dynamic biomarker for monitoring minimal residual disease (MRD) and predicting recurrence in postoperative non-small cell lung cancer (NSCLC) patients. The primary objective is to determine whether serial methylation assessment can guide personalized adjuvant therapy decisions by identifying high-risk individuals, thereby potentially reducing overtreatment or undertreatment. Stage I-IV NSCLC patients undergoing surgical resection were enrolled. Peripheral blood was collected longitudinally for circulating tumor DNA (ctDNA) methylation testing: preoperatively, postoperatively at 3 days, 1, 3, 6, 9, 12, 18, and 24 months, and upon radiographic recurrence. The dynamic changes in SHOX2/PTGER4 methylation levels and conventional tumor marker positivity rates were analyzed. Comprehensive statistical analyses were performed: Correlation between methylation levels and radiographic findings was assessed using Pearson/Spearman tests; predictive accuracy for recurrence was evaluated via ROC curve analysis; patients were stratified into methylation-based risk groups; survival differences were compared using Kaplan-Meier curves with log-rank testing; independent predictive value was determined through multivariate Cox regression adjusting for clinicopathological confounders. Final efficacy assessment integrated ctDNA positivity timing, disease-free survival (DFS), and overall survival (OS) metrics. This prospective biomarker study seeks to validate a novel epigenetic approach for postoperative management, potentially establishing ctDNA methylation monitoring as a standardized tool for MRD detection and recurrence risk stratification in resected NSCLC.

Conditions

Lung Cancer (NSCLC)

Keywords

cfDNA; Methylation biomarker; SHOX2; PTGER4; Surgery; MRD monitoring; Prognostic monitoring

Outcome Measures

Primary Outcomes (3)

• The median lead time of SHOX2/PTGER4 methylation compared with traditional methods (tumor markers, imaging) for prediction.

  Measure time point of outcome: Preoperatively, 3 days, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months postoperatively, and at the time of recurrence. Measure method: SHOX2/PTGER4 Methylation Detection Kit (PCR Fluorescence Method).

  Through study completion, an average of 2 years.

• Disease-free survival: Differences in DFS based on methylation status after treatment.

  Measure time point of outcome: Preoperatively, 3 days, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months postoperatively, and at the time of recurrence. Measure method: Kaplan-Meier method.

  Through study completion, an average of 2 years.

• Dynamic concentration changes: The relative change rate of methylation levels before and after treatment and during recurrence.

  Measure time point of outcome: Preoperatively, 3 days, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months postoperatively, and at the time of recurrence. Measure method: SHOX2/PTGER4 Methylation Detection Kit (PCR Fluorescence Method).

  Through study completion, an average of 2 years.

Secondary Outcomes (3)

• The rate of methylation "turning negative" after treatment

  Through study completion, an average of 2 years.

• The relationship between methylation status and overall survival.

  Through study completion, an average of 2 years.

• Forecast performance

  Through study completion, an average of 2 years.

Study Arms (1)

Surgical treatment group

Patients treated with conventional surgical operations

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with non-small cell lung cancer (NSCLC) diagnosed by histopathology/ clinical diagnosis and scheduled for surgical treatment were selected, with ages ranging from 18 to 85 years old. All enrolled patients had peripheral blood drawn within one week before treatment, and at 3 days, 1 month, 3 months, 6 months, 12 months, 18 months and 24 months after treatment for the detection of SHOX2/PTGER4 methylation in plasma cell-free DNA DNA (cfDNA)

You may qualify if:

• Diagnosed with non-small cell lung cancer (NSCLC) by histopathology/clinical diagnosis.
• Age 18-85 years old.
• Lung cancer patients who are determined by clinicians to be eligible for surgical treatment.
• ECOG score ≤ 2, with an expected survival period of ≥ 6 months, and having signed the informed consent form.
• The subjects should have clear case information, including age, gender, and clinical diagnosis, etc.

You may not qualify if:

• Patients with a history of other malignant tumors or autoimmune diseases.
• Those with severe heart, lung or vascular diseases that make them unable to tolerate surgery.
• Pregnant or lactating women.
• Patients who may be unable to complete follow-up during the study, as well as other factors that the researcher deems inappropriate for participation in the study.
• Incomplete clinical or follow-up information.

Sponsors & Collaborators

• Beijing Haidian Hospital: lead

Study Sites (1)

Beijing Haidian Hospital

Beijing, Beijing Municipality, 100080, China

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral Blood

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Study Officials

• Yuqing Huang

  Beijing Haidian Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yuqing Huang, Ph.D

CONTACT

+86 13371735630; huangyuqing555@qq.com

Hui Liu, Ph.D

CONTACT

+86 82693657; hdyyllbgs@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: December 2, 2025
• Study Start: April 2, 2025
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: December 2, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)