Identifies microtubule-binding protein CSPP1 as a novel cancer biomarker associated with ferroptosis and tumor microenvironment

Abstract

Centrosome and spindle pole-associated protein (<i>CSPP1</i>) is a centrosome and microtubule-binding protein that plays a role in cell cycle-dependent cytoskeleton organization and cilia formation. Previous studies have suggested that <i>CSPP1</i> plays a role in tumorigenesis; however, no pan-cancer analysis has been performed. This study systematically investigates the expression of <i>CSPP1</i> and its potential clinical outcomes associated with diagnosis, prognosis, and therapy. <i>CSPP1</i> is widely present in tissues and cells and its aberrant expression serves as a diagnostic biomarker for cancer. <i>CSPP1</i> dysregulation is driven by multi-dimensional mechanisms involving genetic alterations, DNA methylation, and miRNAs. Phosphorylation of CSPP1 at specific sites may play a role in tumorigenesis. In addition, <i>CSPP1</i> correlates with clinical features and outcomes in multiple cancers. Take brain low-grade gliomas (LGG) with a poor prognosis as an example, functional enrichment analysis implies that <i>CSPP1</i> may play a role in ferroptosis and tumor microenvironment (TME), including regulating epithelial-mesenchymal transition, stromal response, and immune response. Further analysis confirms that <i>CSPP1</i> dysregulates ferroptosis in LGG and other cancers, making it possible for ferroptosis-based drugs to be used in the treatment of these cancers. Importantly, <i>CSPP1</i>-associated tumors are infiltrated in different TMEs, rendering immune checkpoint blockade therapy beneficial for these cancer patients. Our study is the first to demonstrate that <i>CSPP1</i> is a potential diagnostic and prognostic biomarker associated with ferroptosis and TME, providing a new target for drug therapy and immunotherapy in specific cancers.