Department of Clinical Pathomorphology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-094 Bydgoszcz, Poland.
Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-092 Bydgoszcz, Poland.
Int J Mol Sci. 2022 Feb 5;23(3):1819. doi: 10.3390/ijms23031819.
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, 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 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.
纺锤体装置卷曲螺旋蛋白 1(SPDL1)是一种相对较新鉴定的卷曲螺旋结构域蛋白,通过确保有丝分裂的忠实性,成为 DNA 保真度的重要决定因素。因此,SPDL1 被怀疑是人类癌症中基因组(不)稳定性的基础,但它在这些疾病中的确切作用在很大程度上仍未得到探索。鉴于基因组不稳定性(GIN)是结直肠癌(CRC)的一个关键特征,我们主要询问这种蛋白质的表达是否可以解释 CRC 患者的临床病理特征和生存率的差异。通过机构组织微阵列(TMA)中的免疫组织化学评估蛋白质表达,并通过分析公共数据集评估基因表达。为了将预后相关性置于预测的生物学背景中,通过公共数据挖掘鉴定的围绕 SPDL1 的基因共表达集进行注释,并评估其在基因本体论(GO)类别、BRITE 层次结构和 Reactome 途径中的富集情况。与相邻正常组织的比较显示,SPDL1 蛋白在肿瘤病例的一个亚组中高表达(48.84%),即使在调整多个混杂因素后,这些患者的预后也比 SPDL1 低表达的患者好。肿瘤内的 SPDL1 高表达与中位 56 个月的生存优势相关,但与我们队列的任何临床病理特征无关。在 TCGA 队列中,在肿瘤组织中过表达,并与改善的生存、染色体不稳定性表型和各种 GIN 标志物呈正相关。除了细胞周期和有丝分裂中关键的基因外,与 共表达的基因集还包含染色体分离和 DNA 复制的检查点成员,以及与 DNA 修复缺陷和逆行囊泡介导的运输相关的成员。总之,SPDL1 是 CRC 患者生存的独立预测因子,可能与染色体不稳定性有关。