A Potent Multi-Omics Signature for Predicting Recurrence in Patients with Non-Small Cell Lung Cancer after Surgery

Background: study has integrated multiple levels of biological datasets to predict outcome in lung cancer patients. We aimed to develop and validate a prognostic model integrating copy number variation (CNV), DNA methylation, mRNA, and miRNA expression data to predict recurrence in patients with stage I-IIIA non-small cell lung cancer (NSCLC) after surgery. Methods: 509 NSCLC patients with the clinical and four types omics data collected from The Cancer Genome Atlas database were assigned into the discovery (n=237) and validation (n=272) cohorts according to resource of cases. We adopted principal component analysis to reduce the dimension of multi-omics data, and built a multi-omics signature for resected NSCLC using the LASSO Cox regression model. We assessed the predictive ability of the signature with the Harrell's concordance index (C-index). Findings: We built a multi-omics signature (MOSLC) based on 5 CNVs, 14 DNA methylations, 2 miRNAs, and 27 miRNAs. Using this signature, patients were classified into high- or low-risk groups with significant differences in recurrence-free survival in the discovery (hazard ratio [HR] 5.81, 95%CI 3.74-9.03; P<.001), and validation (HR: 2.73, 95%CI 1.78-4.18; P<.001) cohorts. Additionally, the MOSLC showed better predictive performance than the tumor-node-metastasis stage in the discovery (C-index: 0.753 vs. 0.636, P = .002) and validation (0.707 vs. 0.641, P =.098) cohorts. Interpretation: MOSLC is a reliable tool in predicting recurrence for patients with NSCLC, individualizing treatment and follow-up schedule. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (No. 81672872 and No. 81472386). The collection of cancer data used in this study was supported by The Cancer Genome Atlas pilot project established by the National Cancer Institute. Declaration of Interests: The authors stated: No potential conflicts of interest were disclosed. Ethics Approval Statement: Missing.