Overexpression of BMP1 reflects poor prognosis in clear cell renal cell carcinoma

Cancer Gene Ther. 2020 May;27(5):330-340. doi: 10.1038/s41417-019-0107-9. Epub 2019 Jun 3.

Abstract

Clear cell renal cell carcinoma (ccRCC) is the highest mortality, invasion, and metastasis subtype of renal cell carcinoma. Bone morphogenetic protein (BMP) family has recently emerged as a group of cancer-related proteins in multiple pathogenesis of cancers. Currently, little is known about the prediction role of BMPs in ccRCC. Therefore, we screened The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) database for ccRCC patients with complete clinical information and BMP family expression data. Multivariate analysis showed that high expression of BMP1 was associated with shorter overall survival (OS) (P = 0.001), and shorter disease-free survival (DFS) (P = 0.018). Gene set enrichment analysis (GSEA) showed BMP1 was associated with epithelial-mesenchymal transition (EMT), G2M checkpoint, angiogenesis, hypoxia pathway, and Kirsten rat sarcoma viral oncogene (KRAS) signaling. Knockdown BMP1 suppressed malignancy of ccRCC in vitro and in vivo. Our results indicated that high expressions of BMP1 were poor prognostic factors and gene therapy could be an effective treatment for ccRCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics*
  • Bone Morphogenetic Protein 1 / genetics
  • Bone Morphogenetic Protein 1 / metabolism*
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / surgery
  • Cell Line, Tumor
  • Datasets as Topic
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Follow-Up Studies
  • G2 Phase Cell Cycle Checkpoints / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Kaplan-Meier Estimate
  • Kidney / pathology
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / surgery
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Recurrence, Local / epidemiology*
  • Neoplasm Recurrence, Local / genetics
  • Nephrectomy
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • BMP1 protein, human
  • Bone Morphogenetic Protein 1
  • Proto-Oncogene Proteins p21(ras)