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. 2021 Jun 19:29:100377.
doi: 10.1016/j.jbo.2021.100377. eCollection 2021 Aug.

Evaluation of local and circulating osteopontin in malignant and benign primary bone tumors

Ali Nazarizadeh  1 , Shahin Alizadeh-Fanalou  1 , Ameinh Hosseini  1 , Alireza Mirzaei  2 , Vahid Salimi  3 , Hadi Keshipour  4 , Banafsheh Safizadeh  1 , Khodamorad Jamshidi  2 , Mehrdad Bahrabadi  2 , Masoumeh Tavakoli-Yaraki  1
Affiliations

Evaluation of local and circulating osteopontin in malignant and benign primary bone tumors

Ali Nazarizadeh et al. J Bone Oncol. .

Abstract

Purpose: The development of novel and efficient biomarkers for primary bone cancers is of grave importance.

Methods: The expression pattern of osteopontin (OPN) was investigated in the 153 patients with benign (n = 72) and malignant (n = 81) primary bone cancers. Both local and circulating OPN mRNA expression levels and their protein concentration in serum and tumor site were assessed using real-time qRT-PCR, ELISA, and immunohistochemistry techniques, respectively. As a control, 29 healthy individuals were considered. The number of 153 tumor tissue specimens and the 153 paired margins were taken on surgical resection from the patients. 153 blood samples were also drained from all participants, then peripheral blood mononuclear cells (PBMC) and sera were separated.

Results: The mean mRNA expression was significantly higher in all of the cancerous tissues than the paired margins and the PBMC of the patients than the controls. Consistently, the protein concentrations of OPN in serum and tumor tissues were significantly higher in the patients. Furthermore, the malignant cases had significantly elevated the mRNA levels and the protein compared to the benign cases. OPN could potentially differentiate the patients from the controls with 100% sensitivity and specificity in serum. Moreover, OPN could predict some of the malignant cases' clinicopathological features, including metastasis, recurrence, grade, and response to chemotherapy.

Conclusions: In conclusion, OPN might be involved in the pathogenesis of primary bone tumors and can be considered as a potential biomarker to bone cancer diagnosis.

Keywords: ANOVA, One-way analysis of variance; AUC, area under the curve; Bone tumors; CI, confidence interval; Chondrosarcoma; DAPI, 4′,6-Diamidine-2′-phenylindole dihydrochloride; ELISA, Enzyme-linked immunosorbent assay; EMT, epithelial-mesenchymal transition; Ewing Sarcoma; HIF-1α, hypoxia-inducible factor-1 alpha; HRP, horseradish peroxidase; MMP9, Matrix metallopeptidase 9; OCT, Optimal Cutting Temperature; OPN, Osteopontin; Osteopontin; Osteosarcoma; PBMC, Peripheral blood mononuclear cells; PBS, phosphate-buffered saline; ROC, receiver operating characteristic; S100A8, S100 calcium-binding protein A8; SOX9, SRY-Box Transcription Factor 9; cDNA, Complementary DNA; qRT-PCR, Quantitative Real-time transcription-polymerase chain reaction.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Comparison of the diagnostic potential of OPN to differentiate between malignant and benign patients.
Fig. 2
Fig. 2
The assessed OPN mRNA expression levels in tumor for the different clinicopathological variables in the patients with malignant bone cancers The OPN mRNA expression level was evaluated in different types of malignant bone tumors including osteosarcoma (a), Ewing sarcoma(b), and chondrosarcoma (c) for the different clinicopathological variables (chemotherapy status, tumor grade, tumor metastasis, and recurrent) in the patients. The Statistical differences between groups are shown by P values.
Fig. 3
Fig. 3
The assessed OPN mRNA expression levels in PBMC for the different clinicopathological variables in the patients with malignant bone cancers. The OPN mRNA expression level was evaluated in PBMC of patients in different types of malignant bone tumors including osteosarcoma (a), Ewing sarcoma(b) and chondrosarcoma (c) for the different clinicopathological variables (chemotherapy status, tumor grade, tumor metastasis and recurrent) in the patients. The Statistical differences between groups are shown by P values.
Fig. 4
Fig. 4
The assessed OPN protein expression levels in serum for the different clinicopathological variables in the patients with malignant bone cancers The OPN protein level in serum was evaluated in patients with different types of malignant bone tumors including osteosarcoma (a), Ewing sarcoma(b) and chondrosarcoma (c) for the different clinicopathological variables (chemotherapy status, tumor grade, tumor metastasis and recurrent) in the patients. The Statistical differences between groups are shown by P values.
Fig. 5
Fig. 5
The OPN protein level in primary bone tumors. The OPN differential protein expression was assessed in different bone tumor and margin tissues and the OPN expression level was indicated as the percentage of positive reactivity. Representative images showing the expression of OPN in normal bone tissue; with < 10% immunoreactivity, ×100 (a), tumor tissue; with 32% immunoreactivity, ×100.,(b), tumor tissue; with 44% immunoreactivity, ×100.(c), tumor tissue with 53.6% immunoreactivity, ×100.(d) and tumor tissue with 57.1% immunoreactivity, ×100.(e). The OPN protein expression pattern in malignant, benign and margin tissues is shown (f). The Statistical differences between groups are shown by P values.
Fig. 6
Fig. 6
The OPN protein expression in patients with different malignant bone tumors. The protein level of OPN in tumor tissues of patients with different types of malignant bone tumors was assessed. The over-expression of OPN was detected in chemotherapy positive, high- grade, metastatic and recurrent tumors in osteosarcoma (a), Ewing sarcoma(b) and chondrosarcoma (c). The Statistical differences between groups are shown by P values.
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