Correlation of exosomal microRNA clusters with bone metastasis in non-small cell lung cancer
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RESEARCH PAPER
Correlation of exosomal microRNA clusters with bone metastasis in non‑small cell lung cancer Xiao‑Rong Yang1 · Can Pi1 · Ruoying Yu2 · Xiao‑Jun Fan2 · Xiao‑Xiao Peng1 · Xu‑Chao Zhang1 · Zhi‑Hong Chen1 · Xue Wu2 · Yang Shao3,4 · Yi‑Long Wu1 · Qing Zhou1 Received: 16 July 2020 / Accepted: 1 November 2020 © The Author(s) 2020
Abstract 20–40% of lung cancer patients develop bone metastasis (BM) with significantly decreased overall survival. Currently, BM is mainly diagnosed by computerized tomography (CT) scan or magnetic resonance imaging (MRI) when symptom develops. Novel biomarkers with higher prediction value of BM are needed. Plasma-derived exosomal microRNAs had been isolated and sequenced of total 30 non-small cell lung cancer (NSCLC) patients including 16 with bone metastasis and 14 without bone metastasis. Hierarchical clustering based on the total miRNA profile can clearly separate cancer patients and healthy individuals (H), but not patients with (BM +) or without (BM−) BM. Weight Co-expression network of miRNAs (WGCNA) analyses 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. Pathway analysis of cluster B miRNAs revealed enrichment in metabolic pathways that may involve in preconditioning of the metastatic niche. 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. 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 epithelial-mesenchymal transition (EMT) and bone metastasis. Keywords Plasma-derived exosomal microRNAs · NSCLC · Bone metastasis · Wnt/β-catenin pathway · WGCNA
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10585-020-10062-y) contains supplementary material, which is available to authorized users. * Qing Zhou [email protected] 1
Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital & Guangdong Academy of Medical Sciences, School of Medicine, South China University of Technology, Guangzhou, China
2
Geneseeq Technology Inc., Toronto, ON, Canada
3
Nanjing Geneseeq Technology Inc., Nanjing, Jiangsu, China
4
School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
Lung cancer is the leading cause of cancer death worldwide and non-small cell lung cancer (NSCLC) which account for 80% of lung cancers [1] is one of the most common tumors metastasizing to bone. Bone is a common site of blood metastasis and the incidence of bone metastasis (BM) in NSCLC during d
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