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Updated: Jun 4, 2026
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Heavy metal burden and metallothionein-2A expression in relation to severity and short-term outcome in primary
Salma Siddiqui1, Sabir Ali2, Ajai Singh1
1Paediatric Orthopaedics, KGMU, Lucknow, India.
Background:
Osteosarcoma remains the most common primary malignant bone tumor in adolescents and young adults, with survival plateauing despite multimodality therapy. Environmental heavy metals such as lead (Pb) and cadmium (Cd) and their binding protein metallothionein-2A (MT2A) may influence tumor biology, chemoresistance and outcome, but clinical data are scarce.
Methods:
A total of 100 patients with newly diagnosed, histologically confirmed primary osteosarcoma were enrolled in this prospective single-arm cohort at a tertiary referral centre. Clinicopathological details (AJCC grade, stage, tumor size, metastasis) and outcomes (2-3-year survival) were recorded. Blood and tumor tissue were collected at diagnosis; blood was re-sampled after neoadjuvant chemotherapy (NACT), at surgery and after adjuvant chemotherapy (ACT). Pb and Cd were quantified in blood and bone by inductively coupled plasma-optical emission spectrometry. MT2A mRNA was measured by quantitative RT-PCR and MT2A protein by Western blot in blood and tumor. Associations with baseline clinicopathological severity and short-term outcome were analysed.
Results:
Most patients had high-grade (G2) disease and stage IIB tumors; 9% died within 2-3 years. Mean blood Pb and Cd were elevated, with marked skeletal accumulation. MT2A mRNA and protein were significantly up-regulated at diagnosis in both blood and tissue and declined stepwise after NACT, surgery and ACT (p < 0.0001). Baseline blood MT2A mRNA strongly correlated with disease severity (r ≈ 0.82, p < 0.0001) and moderately with mortality, while Pb and Cd showed low-to-moderate positive correlations with both severity and mortality.
Conclusion:
Heavy-metal burden and dynamic MT2A expression were associated with clinicopathological severity and short-term outcome in primary osteosarcoma. These findings should be considered exploratory and require validation in controlled studies with longer follow-up and multivariable modelling before prognostic application.
