To Conduct Multi-omics Integrated Studies in Peripheral Blood, Such as Fragment Omics, Metabolomics and Epigenetics, and Establish Non-invasive Dynamic Follow-up Monitoring Programs During Perioperative and Postoperative Periods (Observational Study)

This project is a prospective observational study designed to comprehensively integrate plasma metabolomic, radiomic, and epigenomic data to develop a predictive model for postoperative recurrence risk in lung cancer. The study will retrospectively enroll 200 patients who underwent radical surgery after neoadjuvant therapy, and prospectively enroll 100 additional post-radical-surgery lung cancer patients who received neoadjuvant treatment as a validation cohort. Peripheral blood samples will be collected at multiple timepoints for metabolomic profiling. Unsupervised clustering, random forest algorithms, and Wilcoxon tests will be applied to identify recurrence-related features and construct a recurrence prediction model.Additionally, using preoperative and first postoperative follow-up CT imaging data, a deep learning-based 3D ResNet will be employed to generate radiomic recurrence risk scores for each patient. Plasma cfDNA will undergo low-pass whole-genome sequencing and methylation analysis to extract multi-dimensional recurrence-associated features. Finally, the study will innovatively utilize the DeepProg deep learning framework to integrate radiomic, cfDNA, and plasma metabolomic data into a non-invasive multi-omics model. Combined with survival data, this model will predict recurrence risk, ultimately achieving high-accuracy stratification of patients' postoperative recurrence probability.

Inclusion criteria

• Signed written informed consent.
• Male or female, aged ≥ 18 and < 85 years.
• Radical resection performed, pathologic stage IB-IIIA (8th TNM) non-small-cell lung cancer.
• Tumor tissue and blood samples obtainable at all protocol-specified time-points.
• No pure ground-glass nodule on imaging.
• Completed standard neoadjuvant immunotherapy combined with platinum-based chemotherapy.

Exclusion criteria

• Postoperative pathology shows other than NSCLC, including but not limited to benign lesions, small-cell carcinoma, metastasis, or indeterminate/inadequate histology.
• Insufficient or poor-quality blood or tissue samples.
• Pure ground-glass nodule on imaging.
• History of any malignancy within the past 5 years.
• Contraindication to surgery preventing radical resection.
• Non-radical (R2) resection.
• Pathologic stage IIIB-N3, IIIC, or IV on paraffin sections.
• Refusal or withdrawal of informed consent.
• Any condition deemed unsuitable by the investigator (e.g., perioperative blood transfusion, severe psychiatric disorder precluding follow-up).