Association of survivin positive circulating tumor cell levels with immune escape and prognosis of osteosarcoma.

ABSTRACT

PURPOSE: Function of survivin protein (encoded by BIRC5) in circulating tumor cells (CTCs) of osteosarcoma (OS) has not been investigated. The goal of this study is to determine whether the expression of survivin protein of CTCs is associated with circulating immune cell infiltration and disease prognosis of OS. METHODS: Blood samples of 20 patients with OS were collected. CanPatrol™ CTC enrichment technology combined with in situ hybridization (ISH) was applied to enrich and test CTCs and survivin protein. Bioinformation analysis combined with data of routine blood test was used to verify the association between survivin and immune cell infiltration in circulatory system. To screen independent prognostic factors, Kaplan-Meier survival curve, univariate and multivariable Cox regression analyses were performed. RESULTS: Bioinformatics analysis showed that BIRC5 was strongly negatively related to lymphocyte, including T cell, NK cell and B cell, which released that BIRC5 played a key role in immune escape via reducing immune cell infiltration in circulatory system. Meanwhile, the number of survivin+ CTCs was significantly negatively connection with lymphocyte count (R = -0.56, p = 0.011), which was consistent with bioinformatics analysis. Kaplan-Meier curve showed that the overall survival rate in high survivin+ CTCs group was significantly lower than low group (88.9% vs 36.4%, p = 0.04). Multivariable Cox regression analyses showed that survivin+ CTCs were an independent prognostic factor (p = 0.019). CONCLUSION: These findings suggested that survivin protein played a key role in immune escape of CTCs and the presence of survivin+ CTCs might be a promising prognostic factor in OS patients.