SKA1/2/3 Serves As a Biomarker for Poor Prognosis in Human Lung Adenocarcinoma

Overview

Journal Transl Lung Cancer Res

Date 2020 May 19

PMID 32420061

Citations 20

Authors

Cheng Chen

Qiang Guo

Yongxiang Song

Gang Xu

Lunxu Liu

Affiliations

Soon will be listed here.

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.

Citing Articles

link to poor prognosis and immune infiltration of head and neck squamous cell carcinomas.

Zhang C, Ke J, Li J, Cai Q Transl Cancer Res. 2024; 13(11):6057-6069.

PMID: 39697720 PMC: 11651734. DOI: 10.21037/tcr-24-862.

SKA1/2/3 is a prognostic and predictive biomarker in esophageal adenocarcinoma and squamous cell carcinoma.

Zhang L, Wang S, Wang L BMC Cancer. 2024; 24(1):1480.

PMID: 39614199 PMC: 11607974. DOI: 10.1186/s12885-024-13257-8.

Identification of an Exosome-relevant SNHG6-hsa-miR-429- CHRDL1/CCNA2 Axis for Lung Adenocarcinoma Prognosis Evaluation.

Yuan Y, Li Q, Chen F, Zhao Y, Ma J, Fang S Curr Med Chem. 2024; 31(28):4549-4561.

PMID: 38994652 DOI: 10.2174/0109298673280925231122104717.

LINC00963 Promotes Cisplatin Resistance in Esophageal Squamous Cell Carcinoma by Interacting with miR-10a to Upregulate SKA1 Expression.

Hu D, Ma A, Lu H, Gao Z, Yu Y, Fan J Appl Biochem Biotechnol. 2024; 196(10):7219-7232.

PMID: 38507172 DOI: 10.1007/s12010-024-04897-4.

Surrogate Biomarker Prediction from Whole-Slide Images for Evaluating Overall Survival in Lung Adenocarcinoma.

Murchan P, Baird A, Broin P, Sheils O, Finn S Diagnostics (Basel). 2024; 14(5).

PMID: 38472935 PMC: 10930763. DOI: 10.3390/diagnostics14050462.

References

Gaitanos T, Santamaria A, Jeyaprakash A, Wang B, Conti E, Nigg E . Stable kinetochore-microtubule interactions depend on the Ska complex and its new component Ska3/C13Orf3. EMBO J. 2009; 28(10):1442-52. PMC: 2669960. DOI: 10.1038/emboj.2009.96. View

Hu R, Wang M, Niu W, Wang Y, Liu Y, Liu L . SKA3 promotes cell proliferation and migration in cervical cancer by activating the PI3K/Akt signaling pathway. Cancer Cell Int. 2018; 18:183. PMC: 6236911. DOI: 10.1186/s12935-018-0670-4. View

Zhang Q, Qi S, Wang Z, Yang C, Wei Y, Chen L . Localization and function of the Ska complex during mouse oocyte meiotic maturation. Cell Cycle. 2012; 11(5):909-16. DOI: 10.4161/cc.11.5.19384. View

Yamada Y, Arai T, Kojima S, Sugawara S, Kato M, Okato A . Anti-tumor roles of both strands of the duplex: their targets and are involved in the pathogenesis of renal cell carcinoma. Oncotarget. 2018; 9(42):26638-26658. PMC: 6003567. DOI: 10.18632/oncotarget.25410. View

Lange K, Suleman A, Srayko M . Kinetochore Recruitment of the Spindle and Kinetochore-Associated (Ska) Complex Is Regulated by Centrosomal PP2A in . Genetics. 2019; 212(2):509-522. PMC: 6553828. DOI: 10.1534/genetics.119.302105. View

Chiba R, Morikawa N, Sera K, Ishida K, Nagashima H, Shigeeda W . Elemental and mutational analysis of lung tissue in lung adenocarcinoma patients. Transl Lung Cancer Res. 2019; 8(Suppl 3):S224-S234. PMC: 6894994. DOI: 10.21037/tlcr.2019.08.18. View

Zhao L, Yang H, Li K, Gao Y, Dong K, Liu Z . Knockdown of SKA1 gene inhibits cell proliferation and metastasis in human adenoid cystic carcinoma. Biomed Pharmacother. 2017; 90:8-14. DOI: 10.1016/j.biopha.2017.03.029. View

Ren Z, Yang T, Zhang P, Liu K, Liu W, Wang P . SKA2 mediates invasion and metastasis in human breast cancer via EMT. Mol Med Rep. 2018; 19(1):515-523. DOI: 10.3892/mmr.2018.9623. View

Weber M, McWilliams A, Canfell K . Prospects for cost-effective lung cancer screening using risk calculators. Transl Cancer Res. 2022; 8(Suppl 2):S141-S144. PMC: 8799126. DOI: 10.21037/tcr.2018.12.08. View

10.

Yu H, Zhang S, Ibrahim A, Deng Z, Wang M . RETRACTED: Serine/threonine kinase BUB1 promotes proliferation and radio-resistance in glioblastoma. Pathol Res Pract. 2019; 215(8):152508. DOI: 10.1016/j.prp.2019.152508. View

11.

Chuang T, Wang J, Jao S, Wu C, Chen J, Hsiao K . Over-expression of AURKA, SKA3 and DSN1 contributes to colorectal adenoma to carcinoma progression. Oncotarget. 2016; 7(29):45803-45818. PMC: 5216762. DOI: 10.18632/oncotarget.9960. View

12.

Theis M, Slabicki M, Junqueira M, Paszkowski-Rogacz M, Sontheimer J, Kittler R . Comparative profiling identifies C13orf3 as a component of the Ska complex required for mammalian cell division. EMBO J. 2009; 28(10):1453-65. PMC: 2684023. DOI: 10.1038/emboj.2009.114. View

13.

Tang D, Zhao X, Zhang L, Wang Z, Wang C . Identification of hub genes to regulate breast cancer metastasis to brain by bioinformatics analyses. J Cell Biochem. 2018; 120(6):9522-9531. DOI: 10.1002/jcb.28228. View

14.

Auckland P, Clarke N, Royle S, McAinsh A . Congressing kinetochores progressively load Ska complexes to prevent force-dependent detachment. J Cell Biol. 2017; 216(6):1623-1639. PMC: 5461014. DOI: 10.1083/jcb.201607096. View

15.

Shen L, Yang M, Lin Q, Zhang Z, Miao C, Zhu B . SKA1 regulates the metastasis and cisplatin resistance of non-small cell lung cancer. Oncol Rep. 2016; 35(5):2561-8. PMC: 4811391. DOI: 10.3892/or.2016.4670. View

16.

Chu J, Wu S, Xing D . Survivin mediates self-protection through ROS/cdc25c/CDK1 signaling pathway during tumor cell apoptosis induced by high fluence low-power laser irradiation. Cancer Lett. 2010; 297(2):207-19. DOI: 10.1016/j.canlet.2010.05.013. View

17.

Sivakumar S, Gorbsky G . Phosphatase-regulated recruitment of the spindle- and kinetochore-associated (Ska) complex to kinetochores. Biol Open. 2017; 6(11):1672-1679. PMC: 5703607. DOI: 10.1242/bio.026930. View

18.

Jiao X, Hooper S, Djureinovic T, Larsson C, Warnberg F, Tellgren-Roth C . Gene rearrangements in hormone receptor negative breast cancers revealed by mate pair sequencing. BMC Genomics. 2013; 14:165. PMC: 3600027. DOI: 10.1186/1471-2164-14-165. View

19.

Moravcikova E, Krepela E, Donnenberg V, Donnenberg A, Benkova K, Rabachini T . BOK displays cell death-independent tumor suppressor activity in non-small-cell lung carcinoma. Int J Cancer. 2017; 141(10):2050-2061. PMC: 5763244. DOI: 10.1002/ijc.30906. View

20.

Su H, Ren F, Jiang H, Chen Y, Fan X . Upregulation of microRNA-520a-3p inhibits the proliferation, migration and invasion via spindle and kinetochore associated 2 in gastric cancer. Oncol Lett. 2019; 18(3):3323-3330. PMC: 6704319. DOI: 10.3892/ol.2019.10663. View