Abstract
Background: Although weak SWI/SNF related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1) expression is a known diagnostic and prognostic biomarker in several malignancies, its expression and clinical significance in osteosarcoma remain unknown. The aim of the present study was to investigate SMARCB1 expression in osteosarcoma and its clinical significance with respect to chemosensitivity and prognosis.Methods: We obtained 114 specimens from 70 osteosarcoma patients to construct a tissue microarray (TMA) and assess SMARCB1 protein expression via immunohistochemistry (IHC). The mRNA expression of SMARCB1 was in-silico analyzed using open-access RNA sequencing (RNA-Seq) and clinicopathological data provided by the Therapeutically Applicable Research to Generate Effective Treatments on Osteosarcoma (TARGET-OS) project. The correlations between SMARCB1 expression and clinical features were statistically analyzed.Results: Weak SMARCB1 expression occurred in 70% of the osteosarcoma patient specimens in the TMA, and significantly correlated with poor neoadjuvant response as well as shorter overall and progression-free survival (PFS). In addition, mRNA in-silico analysis confirmed that SMARCB1 expression correlates with chemotherapeutic response and prognosis in osteosarcoma patients.Conclusion: To our knowledge, the present study is the first to analyze SMARCB1 expression in osteosarcoma. SMARCB1 may serve as a novel diagnostic and prognostic biomarker in osteosarcoma.
Highlights
Osteosarcoma is the most common primary bone malignancy and most often occurs in children and adolescents[1, 2]
Expression of SMARCB1 in osteosarcoma specimens Among the 114 osteosarcoma patient specimens, nuclear immunostaining intensities varied from no staining (41, 36.0%) to 1+ staining (21, 18.4%), 2+ staining (18, 15.8%), 3+ staining (18, 15.8%), 4+ staining (11, 9.6%), and 5+ staining (5, 4.4%) (Figure 1B)
We further examined SMARCB1 expression in specimens with advanced disease status, and found significantly weaker expression of SMARCB1 compared to specimens enrolled in the primary group (1.0±1.2 versus 1.9 ±1.6, P=0.001) (Figure 2B)
Summary
Osteosarcoma is the most common primary bone malignancy and most often occurs in children and adolescents[1, 2]. The 5year survival rate for osteosarcoma patients has improved from 20% to over 65%, a considerable number of patients develop tumors which metastasize, locally recur, or evolve robust chemoresistance[4, 5]. For these challenging cases, the 5-year overall survival rate decreases to a dismal 11-29%[6]. Weak SMARCB1 expression is a known diagnostic and prognostic biomarker in several malignancies, its expression and clinical significance in osteosarcoma remain unknown. Results: Weak SMARCB1 expression occurred in 70% of the osteosarcoma patient specimens in the tissue microarray, and significantly correlated with poor neoadjuvant response as well as shorter overall and progression-free survival. SMARCB1 may serve as a novel diagnostic and prognostic biomarker in osteosarcoma
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