Siglec-15 as a New Perspective Therapy Target in Human Giant Cell Tumor of Bone

Curr Oncol. 2022 Oct 13;29(10):7655-7671. doi: 10.3390/curroncol29100605.

Abstract

The main features of a giant cell tumor of bone (GCTB) are frequent recurrence and aggressive osteolysis, which leads to a poor prognosis in patients. Although the treatment methods for a GCTB, such as scraping and resection, effectively inhibit the disease, the tendency toward malignant transformation remains. Therefore, it is important to identify new treatment methods for a GCTB. In this study, we first found high Siglec-15 expression in GCTB tissues, which was significantly associated with Campanacci staging and tumor recurrence. In Spearman's analysis, Siglec-15 expression was significantly correlated with Ki-67 levels in tumor tissues. In vitro, the mRNA and protein levels of Siglec-15 were high in GCTB stromal cells (Hs737. T), and Siglec-15 knockdown inhibited the biological characteristics of GCTB stromal cells. The RNA sequencing results enabled a prediction of the downstream genes by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and MCODE analyses, and the findings showed that CXCL8 was significantly regulated by Siglec-15 and might be a promising downstream target gene of Siglec-15. Therefore, Siglec-15 may be a potential immunotherapy target for a GCTB.

Keywords: CXCL8; GO analysis; KEGG analysis; Siglec-15; functional assays; giant cell tumor of bone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Neoplasms* / genetics
  • Giant Cell Tumor of Bone* / genetics
  • Giant Cell Tumor of Bone* / metabolism
  • Giant Cell Tumor of Bone* / pathology
  • Humans
  • Ki-67 Antigen
  • RNA, Messenger
  • Sialic Acid Binding Immunoglobulin-like Lectins

Substances

  • Ki-67 Antigen
  • RNA, Messenger
  • Sialic Acid Binding Immunoglobulin-like Lectins

Grants and funding

This work was supported by several grants from National Natural Science Foundation of China (82173210), Hebei Natural Science Foundation (H2021206176) and outstanding medical talents project supported by Hebei Province in 2022.