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.
Keywords: ACC, adrenocortical carcinoma; BP, biological pathways; BRCA, breast invasive carcinoma; Biomarker; C-index, concordance index; CAF, cancer-associated fibroblasts; CC, cellular component; CESC, cervical squamous cell carcinoma and endocervical adenocarcinoma; CHOL, cholangiocarcinoma; CNA, copy number alteration; COAD, colon adenocarcinoma; CPTAC, Clinical Proteomic Tumor Analysis Consortium; CSPP1; CSPP1, centrosome and spindle pole-associated protein; CTL, cytotoxic T lymphocyte; DEGs, differentially expressed genes; DLBC, diffuse large B-cell lymphoma; DSS, disease-specific survival; EMT, epithelial-mesenchymal transition; ENCORI, Encyclopedia of RNA Interactomes; ESCA, esophageal carcinoma; FAG, ferroptosis-associated gene; FDG, ferroptosis-driver gene; FSG, ferroptosis-suppressor gene; Ferroptosis; GBM, glioblastoma multiforme; GO, Gene Ontology; GSEA, Gene Set Enrichment Analysis; GSVA, gene set variation analysis; GTEx, Genotype-Tissue Expression; HNSC, head and neck squamous cell carcinoma; ICB, immune checkpoint blockade; KEGG, Kyoto Encyclopedia of Genes and Genomes; KICH, kidney chromophobe; KIRC, renal clear cell carcinoma; KM, Kaplan-Meier; LAML, acute myeloid leukemia; LGG, low-grade gliomas; LIHC, liver hepatocellular carcinoma; LUAD, lung adenocarcinoma; LUSC, lung squamous cell carcinoma; MF, molecular functions; MHC, major histocompatibility complex; MSI, microsatellite instability; OS, overall survival; OV, ovarian serous cystadenocarcinoma; PAAD, pancreatic adenocarcinoma; PFI, progression-free interval; PFS, progression-free survival; PRAD, prostate cancer; Pan-cancer; READ, rectum adenocarcinoma; ROC, receiver operating characteristics; SKCM, skin cutaneous melanoma; TCGA, The Cancer Genome Atlas; TGCT, testicular germ cell tumors, STAD, stomach adenocarcinoma; THCA, thyroid cancer; THYM, thymoma; TIDE, Tumor Immune Dysfunction and Exclusion; TIMER, Tumor Immune Estimation Resource; TISIDB, Tumor-Immune System Interactions DataBase; TMB, tumor mutation burden; TME, tumor microenvironment; Tumor microenvironment; UCEC, endometrial cancer uterine corpus endometrial carcinoma; UCS, uterine carcinosarcoma.
© 2022 The Authors. Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.