Deregulated bone morphogenetic proteins and their receptors are associated with disease progression of gastric cancer

Abstract

Bone morphogenetic proteins (BMP) are members of the transforming growth factor β superfamily (TGF-β). BMPs are involved in tumourigenesis and disease progression of certain malignancies. To date, the role played by BMPs in gastric cancer (GC) remains largely unknown. In the present study, we systematically analysed the expression and clinical significance of BMP and BMP receptors (BMPR) in TCGA gastric cancer database and GEO database and explored the possible mechanism of action. BMP5 is reduced in gastric cancer tissues, while ACVRL1, ACVR1, TGFBR1, and BMPR2 were significantly increased in the gastric tumours. BMP3, ACVR1, TGFBR1, BMPR1B (also known as ALK6), TGFBR2 and BMPR2 were significantly associated with poorer overall survival of GC patients. A negative correlation was seen between BMP/BMPR and proliferation markers which was supported by their correlation with the cell cycle promoters and inhibitors. More interestingly, further analyses showed that BMPs and their receptors are positively correlated with matrix metalloproteinases (MMPs), epithelial mesenchymal transition (EMT) markers and stemness in GC. Furthermore, positive correlations were also frequently seen between BMP receptors and markers/regulators of angiogenesis and lymphangiogenesis in the gastric tumours. Taken together, these findings suggest that BMPs play dual roles in GC. They may inhibit proliferation of GC cells. On the other hand, they can also promote disease progression through a promotion of invasion, EMT and stemness. The elevated expression of BMP receptors in GC were also highly associated with tumour associated angiogenesis and lymphangiogenesis which facilitate tumour growth, expansion and spread.

Keywords

• Bone morphogenetic protein
• Gastric cancer
• Prognosis
• Proliferation
• Epithelial mesenchymal transition
• Angiogenesis and lymphangiogenesis