Open Access

SYNPO2 promotes the development of BLCA by upregulating the infiltration of resting mast cells and increasing the resistance to immunotherapy

  • Authors:
    • Gongjie Ye
    • Linglan Tu
    • Zhuduo Li
    • Xiangyu Li
    • Xiaoliang Zheng
    • Yongfei Song
  • View Affiliations

  • Published online on: November 29, 2023     https://doi.org/10.3892/or.2023.8673
  • Article Number: 14
  • Copyright: © Ye et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Synaptopodin 2 (SYNPO2) plays a pivotal role in regulating tumor growth, development and progression in bladder urothelial Carcinoma (BLCA). However, the precise biological functions and mechanisms of SYNPO2 in BLCA remain unclear. Based on TCGA database‑derived BLCA RNA sequencing data, survival analysis and prognosis analysis indicate that elevated SYNPO2 expression was associated with poor survival outcomes. Notably, exogenous SYNPO2 expression significantly promoted tumor invasion and migration by upregulating vimentin expression in BLCA cell lines. Enrichment analysis revealed the involvement of SYNPO2 in humoral immune responses and the PI3K/AKT signaling pathway. Moreover, increased SYNPO2 levels increased the sensitivity of BLCA to PI3K/AKT pathway‑targeted drugs while being resistant to conventional chemotherapy. In in vivo BLCA mouse models, SYNPO2 overexpression increased pulmonary metastasis of 5637 cells. High SYNPO2 expression led to increased infiltration of innate immune cells, particularly mast cells, in both nude mouse model and clinical BLCA samples. Furthermore, tumor immune dysfunction and exclusion score showed that patients with BLCA patients and high SYNPO2 expression exhibited worse clinical outcomes when treated with immune checkpoint inhibitors. Notably, in the IMvigor 210 cohort, SYNPO2 expression was significantly associated with the population of resting mast cells in BLCA tissue following PD1/PDL1 targeted therapy. In conclusion, SYNPO2 may be a promising prognostic factor in BLCA by modulating mast cell infiltration and exacerbating resistance to immune therapy and conventional chemotherapy.
View Figures
View References

Related Articles

Journal Cover

January-2024
Volume 51 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Ye G, Tu L, Li Z, Li X, Zheng X and Song Y: SYNPO2 promotes the development of BLCA by upregulating the infiltration of resting mast cells and increasing the resistance to immunotherapy. Oncol Rep 51: 14, 2024
APA
Ye, G., Tu, L., Li, Z., Li, X., Zheng, X., & Song, Y. (2024). SYNPO2 promotes the development of BLCA by upregulating the infiltration of resting mast cells and increasing the resistance to immunotherapy. Oncology Reports, 51, 14. https://doi.org/10.3892/or.2023.8673
MLA
Ye, G., Tu, L., Li, Z., Li, X., Zheng, X., Song, Y."SYNPO2 promotes the development of BLCA by upregulating the infiltration of resting mast cells and increasing the resistance to immunotherapy". Oncology Reports 51.1 (2024): 14.
Chicago
Ye, G., Tu, L., Li, Z., Li, X., Zheng, X., Song, Y."SYNPO2 promotes the development of BLCA by upregulating the infiltration of resting mast cells and increasing the resistance to immunotherapy". Oncology Reports 51, no. 1 (2024): 14. https://doi.org/10.3892/or.2023.8673