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泛癌分析结合实验探究纺锤体装置卷曲螺旋蛋白1(SPDL1)的致癌作用。

Pan-cancer analysis combined with experiments explores the oncogenic role of spindle apparatus coiled-coil protein 1 (SPDL1).

作者信息

Song Peng, Wusiman Dilinaer, Li Fenglan, Wu Xiaoxuan, Guo Lei, Li Wenbin, Gao Shugeng, He Jie

机构信息

Department of Thoracic Surgery, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Department of Head and Neck Surgery, National Cancer Center, National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

出版信息

Cancer Cell Int. 2022 Jan 29;22(1):49. doi: 10.1186/s12935-022-02461-w.

Abstract

BACKGROUND

The function of spindle apparatus coiled-coil protein 1 (SPDL1) as a cancer-promoting gene has been reported in a number of studies. However, the pan-cancer analysis of SPDL1 is still lacking. Here, we performed this pan-cancer analysis to evaluate the expression and prognostic value of SPDL1 and gain insights into the association between SPDL1 and immune infiltration.

METHODS

In this study, based on the datasets of The cancer genome atlas (TCGA), Gene expression omnibus (GEO), The Genotype-Tissue Expression (GTEx) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), we used R4.1.0 software and the online tools, including TIMER2.0, GEPIA2, cBioPortal, Modbase, UALCAN, MEXPRESS, STRING, Ensembl, NCBI, HPA, Oncomine, PhosphoNET and the Kaplan-Meier plotter, to explore the potential oncogenic roles of SPDL1. The expression of SPDL1 was also further verified by immunohistochemistry (IHC) in lung adenocarcinoma (LUAD) tissues.

RESULTS

SPDL1 was overexpressed in most tumors compared with adjacent normal tissues, and SPDL1 expression was significantly correlated with the prognosis in most tumor types. The main type of genetic mutation of SPDL1 was missense mutation and the frequency of R318Q/W mutation was highest (4/119). The expression of SPDL1 was closely associated with genomic instability. The SPDL1 phosphorylation levels in S555 was enhanced in ovarian cancer. The SPDL1 expression was positively correlated with the immune infiltration of CD8+ T-cells and cancer-associated fibroblasts (CAFs) in most of the tumor types. Nuclear division, organelle fission and chromosome segregation were involved in the functional mechanisms of SPDL1.

CONCLUSIONS

These findings suggested that SPDL1 might serve as a biomarker for poor prognosis and immune infiltration in cancers, shedding new light on therapeutics of cancers.

摘要

背景

多项研究报道了纺锤体装置卷曲螺旋蛋白1(SPDL1)作为促癌基因的功能。然而,目前仍缺乏对SPDL1的泛癌分析。在此,我们进行了这项泛癌分析,以评估SPDL1的表达和预后价值,并深入了解SPDL1与免疫浸润之间的关联。

方法

在本研究中,基于癌症基因组图谱(TCGA)、基因表达综合数据库(GEO)、基因型-组织表达数据库(GTEx)和临床蛋白质组肿瘤分析联盟(CPTAC)的数据集,我们使用R4.1.0软件和在线工具,包括TIMER2.0、GEPIA2、cBioPortal、Modbase、UALCAN、MEXPRESS、STRING、Ensembl、NCBI、HPA、Oncomine、PhosphoNET和Kaplan-Meier绘图仪,来探索SPDL1的潜在致癌作用。还通过免疫组织化学(IHC)在肺腺癌(LUAD)组织中进一步验证了SPDL1的表达。

结果

与相邻正常组织相比,SPDL1在大多数肿瘤中过度表达,并且在大多数肿瘤类型中,SPDL1表达与预后显著相关。SPDL1的主要基因突变类型为错义突变,其中R318Q/W突变频率最高(4/119)。SPDL1的表达与基因组不稳定性密切相关。在卵巢癌中,S555位点的SPDL1磷酸化水平增强。在大多数肿瘤类型中,SPDL1表达与CD8 + T细胞和癌症相关成纤维细胞(CAF)的免疫浸润呈正相关。核分裂、细胞器分裂和染色体分离参与了SPDL1的功能机制。

结论

这些发现表明,SPDL1可能作为癌症预后不良和免疫浸润的生物标志物,为癌症治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3272/8801078/33e2a075c00b/12935_2022_2461_Fig1_HTML.jpg

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