BTK as a novel diagnostic biomarker and therapeutic target in osteosarcoma

  • J Orthop Sci. 2026 Mar 29:S0949-2658(26)00083-7. doi: 10.1016/j.jos.2026.02.016.
Jiude Jia  1 ,  Weihsiang Hung  1 ,  Jinluan Lin  2 ,  Leiting Zhuang  1 ,  Miersalijiang Yasen  1 ,  Jinwang Huang  1 ,  Wenhui Shen  3
Affiliations
  • 1. Department of Orthopaedic Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361000, China.
  • 2. Department of Orthopaedic, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Orthopedics, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China; Fujian Institute of Orthopedics, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, China.
  • 3. Department of Orthopaedic Surgery, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361000, China. Electronic address: [email protected].
PMID: 41912366 DOI: 10.1016/j.jos.2026.02.016
Abstract

Background: Osteosarcoma is the most common malignant bone tumor in adolescents with a poor prognosis. So far, there is still a lack of effective molecular biomarkers for early diagnosis and effective therapeutic targets for osteosarcoma. Bruton tyrosine kinase (Btk) is reported to be overexpressed in various tumors and may be present as an independent prognostic biomarker. The functions of Btk in osteosarcoma are still unclear. Thereby, our study is devoted to investigating the status of Btk in the progression of osteosarcoma.

Methods: An immunohistochemistry (IHC) assay was used to detect the expression of Btk in osteosarcoma tissues. Cell count kit-8 (CCK-8), cell colony, transwell, transcriptome Sequencing, Western blot and xenograft model assays were applied to analyze osteosarcoma biological function changes after blocking by the Btk Inhibitor (Ibrutinib).

Results: The findings showed that Btk is high expressed in osteosarcoma tissues, and high Btk expression predicts poor survival outcome in osteosarcoma patients. Blocking of Btk by Ibrutinib can partially suppress the proliferation, migration, invasion, tumor growth and lung metastasis in osteosarcoma via the NF-κB signaling pathway.

Conclusions: Our present study suggested that Btk may present as a proto-oncogene in the progression of osteosarcoma, and inhibiting Btk expression can partially suppress the progression of osteosarcoma via the NF-κB signaling pathway.

Keywords
BTK; Biomarker; Diagnostics; Osteosarcoma; Therapy.
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