SKA1/2/3作为人类肺腺癌预后不良的生物标志物。

SKA1/2/3 serves as a biomarker for poor prognosis in human lung adenocarcinoma.

作者信息

Chen Cheng, Guo Qiang, Song Yongxiang, Xu Gang, Liu Lunxu

机构信息

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.

Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, China.

出版信息

Transl Lung Cancer Res. 2020 Apr;9(2):218-231. doi: 10.21037/tlcr.2020.01.20.

Abstract

BACKGROUND

Spindle and kinetochore associated complex subunit 1/2/3 (SKA1/2/3), which stabilized spindle microtubules attaching to kinetochore (KT) in the middle stage of mitosis, were dysregulated, and closely related to prognosis in several malignant tumors. Nevertheless, the potential clinical value of SKA1/2/3, especially in terms of prognosis and development of NSCLC, had not been fully elucidated.

METHODS

ONCOMINE, GEPIA, UALCAN, TCGA, STRING and other databases were used to analyze the expression of SKA1/2/3 in patients with lung adenocarcinoma (LUAD) and its clinical value, and to explore the possible regulatory mechanism of SKA in the occurrence and development of LUAD.

RESULTS

In patients with LUAD, SKA1/2/3 mRNA expression level was significantly up-regulated, and AUC was 0.9558, 0.7034 and 0.9775, respectively. Increased SKA 1/2/3 expression was associated with smoking, tissue typing, and poor prognosis in LUAD patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed that SKA1/2/3 was mainly enriched in DNA replication, cell cycle, homologous recombination, p53 signaling pathway, etc. Hub genes in protein-protein interactions are CDK1, BUB1, CCNA2, CDC20, CCNB2, CCNB1, BUB1B, AURKB, TOP2A and MAD2L1. Hub gene expression in LUAD is increased, and its increased expression is related to poor prognosis of LUAD patients. Finally, the expression of SKA1/2/3 and its correlation with clinicopathological features were verified in 30 clinical LUAD samples.

CONCLUSIONS

SKA1/2/3 may serve as a potential prognostic biomarker and target for LUAD. In addition, SKA 1/2/3 may affect the prognosis of LUAD through DNA replication, cell cycle, homologous recombination and p53 signaling pathway.

摘要

背景

纺锤体和动粒相关复合体亚基1/2/3(SKA1/2/3)在有丝分裂中期稳定附着于动粒(KT)的纺锤体微管,其表达失调,且与多种恶性肿瘤的预后密切相关。然而,SKA1/2/3的潜在临床价值,尤其是在非小细胞肺癌(NSCLC)的预后和发展方面,尚未得到充分阐明。

方法

使用ONCOMINE、GEPIA、UALCAN、TCGA、STRING等数据库分析SKA1/2/3在肺腺癌(LUAD)患者中的表达及其临床价值,并探讨SKA在LUAD发生发展中的可能调控机制。

结果

在LUAD患者中,SKA1/2/3 mRNA表达水平显著上调,曲线下面积(AUC)分别为0.9558、0.7034和0.9775。SKA 1/2/3表达增加与LUAD患者的吸烟、组织类型及预后不良相关。基因本体论(GO)和京都基因与基因组百科全书(KEGG)显示,SKA1/2/3主要富集于DNA复制、细胞周期、同源重组、p53信号通路等。蛋白质-蛋白质相互作用中的枢纽基因有细胞周期蛋白依赖性激酶1(CDK1)、BUB1、细胞周期蛋白A2(CCNA2)、细胞分裂周期蛋白20(CDC20)、细胞周期蛋白B2(CCNB2)、细胞周期蛋白B1(CCNB1)、BUB1B、极光激酶B(AURKB)、拓扑异构酶IIα(TOP2A)和有丝分裂后期促进复合物2(MAD2L1)。LUAD中枢纽基因表达增加,其表达增加与LUAD患者预后不良相关。最后,在30例临床LUAD样本中验证了SKA1/2/3的表达及其与临床病理特征的相关性。

结论

SKA1/2/3可能作为LUAD潜在的预后生物标志物和治疗靶点。此外,SKA 1/2/3可能通过DNA复制、细胞周期、同源重组和p53信号通路影响LUAD的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b937/7225159/0d2313f59486/tlcr-09-02-218-f1.jpg

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