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

癌变 癌症研究 肿瘤微环境 生物标志物 生物 间质细胞 癌症 免疫检查点 免疫疗法 医学 免疫系统 免疫学 遗传学 肿瘤细胞
作者
Lei Wang,Jingjing Zhang,Yuqing Wang,Xu Yan,Shirong Zhang
出处
期刊:Computational and structural biotechnology journal [Elsevier BV]
卷期号:20: 3322-3335 被引量:22
标识
DOI:10.1016/j.csbj.2022.06.046
摘要

Centrosome and spindle pole-associated protein (CSPP1) 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 CSPP1 plays a role in tumorigenesis; however, no pan-cancer analysis has been performed. This study systematically investigates the expression of CSPP1 and its potential clinical outcomes associated with diagnosis, prognosis, and therapy. CSPP1 is widely present in tissues and cells and its aberrant expression serves as a diagnostic biomarker for cancer. CSPP1 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, CSPP1 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 CSPP1 may play a role in ferroptosis and tumor microenvironment (TME), including regulating epithelial-mesenchymal transition, stromal response, and immune response. Further analysis confirms that CSPP1 dysregulates ferroptosis in LGG and other cancers, making it possible for ferroptosis-based drugs to be used in the treatment of these cancers. Importantly, CSPP1-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 CSPP1 is a potential diagnostic and prognostic biomarker associated with ferroptosis and TME, providing a new target for drug therapy and immunotherapy in specific cancers.

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