title: Repulsive guidance molecule B inhibits metastasis and is associated with decreased mortality in non-small cell lung cancer.
abstract: Repulsive guidance molecules (RGMs) are co-receptors of bone morphogenetic proteins (BMPs) and programmed death ligand 2 (PD-L2), and might be involved in lung and other cancers. We evaluated repulsive guidance molecule B (RGMB) expression in 165 non-small cell lung cancer (NSCLC) tumors and 22 normal lung tissue samples, and validated the results in an independent series of 131 samples. RGMB was downregulated in NSCLC (P ≤ 0.001), possibly through promoter hypermethylation. Reduced RGMB expression was observed in advanced-stage tumors (P = 0.017) and in tumors with vascular invasion (P < 0.01), and was significantly associated with poor overall survival (39 vs. 62 months, P < 0.001) and with disease-associated patient mortality (P = 0.015). RGMB knockdown promoted cell adhesion, invasion and migration, in both NSCLC cell lines and an in vivo mouse model, which enhanced metastatic potential. Conversely, RGMB overexpression and secretion suppressed cancer progression. The tumor-suppressing effect of RGMB was exerted through inhibition of the Smad1/5/8 pathway. Our results demonstrate that RGMB is an important inhibitor of NSCLC metastasis and that low RGMB expression is a novel predictor or a poor prognosis.
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510530, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Lin
authors.initials: L
authors.lastname: Ye
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510530, China.
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: Shi
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510530, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510530, China.
authors.forename: Fenglan
authors.initials: F
authors.lastname: Feng
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510530, China.
authors.forename: Yaoqi
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Yiren
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510530, China.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Shen
authors.affiliation: Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Cardiff-China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: State Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, National Clinical Research Center for Respiratory Disease, Guangzhou 510530, China.
authors.forename: Jianxing
authors.initials: J
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D005260:Female; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D015816:Cell Adhesion Molecules, Neuronal; C560433:RGMB protein, human
keywords: NSCLC; RGMB; metastasis