Abstract
Background
20–40% of lung cancer patients develop bone metastasis (BM) with significantly decreased overall survival. Currently, BM is mainly diagnosed by CT scan or MRI when symptom develops. Novel biomarkers with higher prediction value of BM are needed.
Methods
Prospective analysis was undertaken on non-small cell lung cancer (NSCLC) patients with (BM+) and without BM (BM-). Plasma exosomal RNA was isolated and sequenced from peripheral blood of patients. Differential expression analysis and weighted gene co-expression networks analysis (WGCNA) of mi-RNA sequencing data were performed between two groups.
Results
Hierarchical clustering based on the total miRNA profile can clearly separate cancer patients and healthy individuals (H), but not patients BM + or BM-. WGCNA identified three consensus clusters (A, B, C) of highly correlated miRNAs, among which cluster B (144 miRNAs) showed significantly differential expression in lung cancer patients, especially in BM + group. Three differentially expressed miRNAs between BM + and BM- patients within cluster B were identified as miR-574-5p, a suppressor of Wnt/β-catenin pathway, was down-regulated, while miR-328-3p and miR-423-3p, two activators of the same pathway, were up-regulated in BM + patients. Pathway analysis of cluster B miRNAs revealed enrichment in metabolic pathways that may involve in preconditioning of the metastatic niche. Cluster A miRNAs (n = 49) also showed trend of upregulation in BM + patients. Interestingly, pathway analysis indicated that 43 of them are associated with chromosome14, which has been suggested to promote EMT and bone metastasis.
Conclusion
These data indicated that a cluster of mi-RNAs showed significantly differential expression in BM + group, including miR-574-5p, miR-328-3p and miR-423-3p.
Osteopontin genetic variants are associated with overall survival in advanced non-small-cell lung cancer patients and bone metastasis
