Associations Between Vitronectin, PD-L1 And Prognosis In Osteosarcoma

Part 1: Vitronectin significantly influences prognosis in osteosarcomaBackground and Purpose: Vitronectin(Vn), a multifunctional adhesive protein, is found in association with tumor progression, angiogenesis and metastasis in a variety of(human) tumors. But no studies concerning its correlation to osteosarcoma prognosis were found. Hence, we aimed to investigate the prognostic value of Vitronectin(Vn) in osteosarcoma.Methods: Here, we studied the expression of VN in the tumor tissues from 67 patients with osteosarcoma and 20 patients with osteochondroma using immunohistochemistry and estimated the effects of VN expression in osteosarcoma on progression-free survival(PFS) and overall survival(OS) using the Kaplan-Meier curve and COX proportional hazards regression model.Results: Increased expression of VN in osteosarcoma tissue compared to no VN expression in osteochondroma tissue was shown in immunohistochemical assay. No associations were observed between VN expression and osteosarcoma patients' gender(P = 0.675), age(P = 0.813), tumor size(P = 0.436), histologic subtype(P = 0.0.543) or tumor location(P = 0.456). Univariate survival analysis demonstrated significant correlations of high VN expression with shorter PFS(P = 0.002) and OS(P = 0.001); multivariate survival analysis revealed high VN expression as a significant independent prognostic indicator for shorter PFS(HR 2.788, P = 0.003) and OS(HR2.817, P = 0.003).Conclusion: the high expression of VN in tumor cells independently indicated poor clinical prognosis in patients with osteosarcoma, other than large tumor size and non-neoadjuvant chemoradiotherapy, suggesting that VN may serve as a potential therapeutic target in osteosarcoma.Part 2: PD-L1 is associated with poor prognosis of osteosarcomaPurpose: To detect PD-L1 expression in 72 osteosarcoma tissues and investigate whether PD-L1 could serve as an independent prognostic indicator for osteosarcoma.Methods: Immunohistochemistry(IHC) was used to detect PD-L1 expression in paraffin-embedded tissues of 72 primary osteosarcoma. Cases showing more than 5% of neoplastic cells expression of PD-L1 were considered positive(+).Results: Of the 72 primary osteosarcoma tissues examined for PD-L1 expression, 22 had positive staining(approximately 30.6%). There were no statistically significant correlations between PD-L1 expression and clinicopathological variables including patient age, gender, tumor location, tumor size, or neoadjuvant chemotherapy treatment(p > 0.05). PD-L1+cases had a worse progression-free survival(PFS, median: 10.0 months, 95% CI: 0.0-20.7; p = 0.011) and overall survival(OS, median: 28.0 months, 95% CI: 11.1-45.0; p = 0.009) than that of PD-L1-cases(PFS, median: 44.0 months, 95% CI: 21.0-67.0; OS, median: 52.0 months, 95% CI: 31.4-72.6). PD-L1+ staining was illustrated as an independent unfavorable prognostic indicator for PFS(HR: 2.377, p =0.009) and OS(HR: 2.342, p = 0.010).Conclusions: Our findings showed that PD-L1 expressed in a subset of primary osteosarcoma, which was associated with poor PFS and OS, indicating that PD-L1 expression could serve as a new indicator of prognosis for osteosarcoma.