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

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

Cheng Chen  1   2 , Qiang Guo  2 , Yongxiang Song  2 , Gang Xu  2 , Lunxu Liu  1
Affiliations

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

Cheng Chen et al. Transl Lung Cancer Res. 2020 Apr.

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.

Keywords: Spindle and kinetochore associated complex subunit (SKA); biomarker; enrichment analysis; lung adenocarcinoma; prognosis.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr.2020.01.20). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
The expression of SKA1/2/3 in Oncomine database in various tumors. Note: red represents up-regulation of the target gene, while blue represents down-regulation of the target gene. Threshold parameter: P value is 1E-4, multiple change is 1.5. SKA1/2/3, spindle and kinetochore associated complex subunit 1/2/3.
Figure 2
Figure 2
Expression of SKA1/2/3 in LUAD patients. (A) Expression of SKA1/2/3 in cBioPortal database in LUAD; (B) expression of SKA1/2/3 in Ualcan database. ***, P<0.001. SKA1/2/3, spindle and kinetochore associated complex subunit 1/2/3; LUAD, lung adenocarcinoma.
Figure 3
Figure 3
The diagnostic value of SKA1/2/3 in LUAD patients. (A) SKA1; (B) SKA2; (C) SKA3. SKA1/2/3, spindle and kinetochore associated complex subunit 1/2/3; LUAD, lung adenocarcinoma.
Figure 4
Figure 4
The relationship of SKA1 (A), SKA2 (B), SKA3 (C) with OS in LUAD patients in GEPIA database. SKA, spindle and kinetochore-associated.
Figure 5
Figure 5
The top 10 genes with positive and negative co-expression of SKA1 (A), SKA2 (B), SKA3 (C) in TCGA database according to Heat map and Venn map. (D) Intersection co-expression genes of SKA1/2/3. Note: |r| >0.4 and P<0.001. SKA, spindle and kinetochore-associated.
Figure 6
Figure 6
GO analysis of SKA1 (A), SKA2 (B), SKA3 (C) co-expression genes, and intersection co-expression genes among with SKA1/2/3 (D). GO, Gene ontology.
Figure 7
Figure 7
KEGG pathway enrichment analysis of SKA1 (A), SKA2 (B), SKA3 (C) co-expression genes, and intersection co-expression genes among with SKA1/2/3 (D). SKA, spindle and kinetochore associated complex subunit. KEGG, Kyoto Encyclopedia of Genes and Genome.
Figure 8
Figure 8
Hub gene expression was increased in LUAD in GEPIA database. The expressions of CDK1 (A), BUB1 (B), CCAN2 (C), BUB1B (D), CCNB2 (E), CDC20 (F), CCNB1 (G), AURKB (H), TOP2A (I), and MAD2L1 (J) were shown. LUAD, lung adenocarcinoma.
Figure S1
Figure S1
The correlations of the representative 10 Hub genes with OS of LUAD patients in the GEPIA database. (A) CDK1; (B) BUB1; (C) CCNA2; (D) BUB1B; (E) CCNB2; (F) CDC20; (G) CCNB1; (H) AURKB; (I) TOP2A; (J) MAD2L1. OS, overall survival; LUAD, lung adenocarcinoma.
Figure S2
Figure S2
The correlations of the representative 10 Hub genes with DFS of LUAD patients in the GEPIA database. (A) CDK1; (B) BUB1; (C) CCNA2; (D) BUB1B; (E) CCNB2; (F) CDC20; (G) CCNB1; (H) AURKB; (I) TOP2A; (J) MAD2L1. DFS, disease-free survival; LUAD, lung adenocarcinoma.
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