Phosphoserine phosphatase as an indicator for survival through potentially influencing the infiltration levels of immune cells in neuroblastoma

磷酸丝氨酸磷酸酶通过潜在影响神经母细胞瘤中免疫细胞的浸润水平作为生存指标

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作者:Liang Zeng, Xiao-Yun Liu, Kai Chen, Liang-Jun Qin, Feng-Hua Wang, Lei Miao, Le Li, Hai-Yun Wang

Conclusion

These findings suggested that PSPH expression could be a promising indicator for prognosis and immunotherapy in neuroblastoma patients by potentially influencing infiltration levels of immune cells.

Methods

The TARGET dataset (n = 151) and our hospital-based cases (n = 55) were used for assessing the expression level of PSPH associated with survival in neuroblastoma patients, respectively. Then, in vitro experiments were performed to define the role of PSPH in neuroblastoma. The ESTIMATE and TIMER algorithms were utilized to examine the correlation between PSPH expression level and abundance of immune cells. Further, Kaplan-Meier survival analysis was performed to evaluate the effect of both PSPH and immune cells on patients' prognosis.

Results

High expression of PSPH was significantly associated with unfavorable overall survival (OS) and event-free survival (EFS) in both the TARGET dataset and our hospital-based cases, and was an independent predictor of OS (hazard ratio, 2.00; 95% confidence intervals, 1.21-3.30, p = 0.0067). In vitro experiments showed that high expression of PSPH significantly promoted cell growth and metastasis. Further, the ESTIMATE result suggested that high expression level of PSPH was negatively associated with low stromal and ESTIMATE score. Specifically, high PSPH expression was found to be negatively associated with CD8+ T cell, macrophages and neutrophils, which negatively affected survival of neuroblastoma patients (p < 0.0001, p = 0.0005, and p = 0.0004, respectively).

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