Kan Wang,1,* Jinxin Wan,2,* Ruipeng Zheng,1,* Yifei Xiao,1 Fengjun Lv,1 Haitao Ge,1 Guang Yang,3 Yu Cheng1 

1Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, 150007, People’s Republic of China; 2Department of Neurosurgery, Guangdong Provincial People’s Hospital, Zhuhai Hospital (Jinwan Central Hospital of Zhuhai), Zhuhai City, Guangdong Province, 519090, People’s Republic of China; 3Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yu Cheng, Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin City, Heilongjiang Province, 150007, People’s Republic of China, Email ccyy30@126.com Guang Yang, Department of Neurosurgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, 362000, People’s Republic of China, Email 151534363@qq.com

Background: Gliomas, including glioblastoma (GBM), present significant treatment challenges due to their poor prognosis and complex tumor microenvironment. This study investigates the role of Secreted Phosphoprotein 1 (SPP1) as a prognostic and immunotherapeutic biomarker in gliomas and other cancers through pan-cancer analysis.
Methods: A comprehensive pan-cancer analysis was conducted using datasets from UCSC TCGA Pan-Cancer, TCGA-GBM, UALCAN, and single-cell sequencing data from GEO and TISCH. The correlation of SPP1 expression with overall survival (OS), progression-free survival (PFS), immune cell infiltration, and immune checkpoint markers was analyzed. Functional validation was performed via SPP1 knockdown in glioma cell lines to evaluate effects on proliferation, invasion, and immune interactions.
Results: SPP1 was found to be overexpressed in 27 tumor types, with high expression correlating with poor OS, PFS, and increased immune cell infiltration, particularly with CD8+ T cells and macrophages. Single-cell analysis indicated SPP1 enrichment in macrophages interacting with malignant GBM cells. Knockdown of SPP1 significantly inhibited glioma cell proliferation, invasion, and promoted apoptosis.
Conclusion: The findings suggest that SPP1 is a promising target for immunotherapy, potentially improving outcomes for patients with gliomas and other cancers. Further research is warranted to explore SPP1-targeted therapies and their efficacy in clinical settings.

Keywords: SPP1, glioblastoma, immunotherapy, biomarker, prognosis