Abstract
Spindle Apparatus Coiled-Coil Protein 1 (SPDL1) is a relatively recently identified coiled-coil domain containing protein and an important determinant of DNA fidelity by ensuring faithful mitosis. Hence, SPDL1 is suspected to underlie genomic (in-)stability in human cancers, yet its exact roles in these diseases remain largely underexplored. Given that genomic instability (GIN) is a crucial feature in colorectal cancer (CRC), we primarily asked whether the expression of this protein may account for differences in clinicopathological features and survival rates of CRC patients. Protein expression was evaluated by immunohistochemistry in the institutional tissue microarray (TMA), and gene expression by the analysis of publicly available datasets. To place the prognostic relevance in a predicted biological context, gene co-expression set around SPDL1 identified by public data mining was annotated and assessed for enrichment in gene ontology (GO) categories, BRITE hierarchies, and Reactome pathways. The comparison with adjacent normal tissue revealed a high expression of SPDL1 protein in a subset of tumor cases (48.84%), and these had better prognosis than the SPDL1-low expression counterpart even after adjustment for multiple confounders. SPDL1-high expression within tumors was associated with a median 56-month survival advantage, but not with any clinicopathological characteristics of our cohort. In the TCGA cohort, SPDL1 was overexpressed in tumor tissue and positively associated with improved survival, chromosome instability phenotype, and various GIN markers. In addition to the genes critically involved in the cell cycle and mitosis, a gene set co-expressed with SPDL1 contained checkpoint members of both chromosome segregation and DNA replication, as well as those associated with defective DNA repair, and retrograde vesicle-mediated transport. In conclusion, SPDL1 is an independent predictor of CRC patient survival in a possible connection with chromosomal instability.
Highlights
According to GLOBOCAN 2020 data, carcinoma of the colon or rectum is the third most commonly diagnosed cancer, and the second leading cause of cancer death worldwide, despite progress made in diagnosis, prognosis and management through surgery, radiotherapy, chemotherapy, and immunotherapy [1,2]
Spindle Apparatus Coiled-Coil Protein 1 (SPDL1) expression was predominantly cytoplasmic in colorectal cancer (CRC), with several tissues showing combined cytoplasmic-membranous (9.30%) or cytoplasmic-nuclear (6.98%) expression
Cytoplasmic SPDL1 was characterized by ubiquitous, diffuse staining on tumor cells but not in a uniform intensity
Summary
According to GLOBOCAN 2020 data, carcinoma of the colon or rectum (colorectal cancer [CRC]) is the third most commonly diagnosed cancer, and the second leading cause of cancer death worldwide, despite progress made in diagnosis, prognosis and management through surgery, radiotherapy, chemotherapy, and immunotherapy [1,2]. Its critical role in mitotic spindle formation and chromosome segregation has been supported by further evidence, and, in addition, SPLD1 s interphase function was proposed [6]. With regard to the latter, this protein was shown to be required for rapid migration of human cells, likely due to its ability to regulate dynein/dynactin activity, similar as in mitosis [6]. The biological significance of SPDL1 was captured based on the functional enrichment analyses through online bioinformatics platforms and web tools
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