J Cancer 2020; 11(10):2921-2934. doi:10.7150/jca.41834

Research Paper

Potential therapeutic targets of the nuclear division cycle 80 (NDC80) complexes genes in lung adenocarcinoma

Zhong-Yi Sun1, Wei Wang1, Han Gao2, Quan-Fang Chen2✉

1. Department of Emergency, the First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.
2. Institute of respiratory disease, the First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, People's Republic of China.

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Citation:
Sun ZY, Wang W, Gao H, Chen QF. Potential therapeutic targets of the nuclear division cycle 80 (NDC80) complexes genes in lung adenocarcinoma. J Cancer 2020; 11(10):2921-2934. doi:10.7150/jca.41834. Available from http://www.jcancer.org/v11p2921.htm

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Abstract

Background: Lung cancer is the most common cancer worldwide, both in terms of the incidence and mortality. NDC80 complex comprising of NDC80, NUF2, SPC24, and SPC25 is a heterotetrameric protein complex located in the outer layer of the kinetochore and plays a critical role in mitosis. This study focuses on the effects of NDC80 complex genes on clinical features and prognosis in lung adenocarcinoma (LUAD).

Materials and methods: Expression of NDC80 complex in LUAD and related clinical information was extracted from the TCGA website. NDC80 complex gene functional analysis and correlation analysis was conducted by using DAVID, BiNGO, Gene MANIA, STRING and GSEA. Survival probability was predicted by nomogram. Statistical analysis was used to predict NDC80 complex gene expression on clinical features and prognosis in patients with LUAD.

Results: Expression of NDC80, NUF2, SPC24 and SPC25 was significantly elevated in LUAD tumors compared with normal tissues (P < 0.05). These genes showed diagnostic values for LUAD (P < 0.001 for each; area under the curve (AUC), 0.958, 0.968, 0.951, and 0.932 respectively); combinatorial analysis of these genes was more advantageous than single analysis alone (P < 0.001; AUC > 0.900 for each). Expression of both NDC80 and SPC25 correlated with the prognosis of LUAD (P < 0.001; AUC > 0.600 for each). Higher expression of NDC80, NUF2, SPC24 and SPC25 was associated with low overall survival (OS) in univariate analysis. Higher expression of NDC80 and SPC25 was associated with low OS in multivariate analysis. High expression of NDC80 combined with high expression of SPC25 was predictive of poor OS in LUAD in joint analysis.

Conclusion: NDC80 complex gene might be an early indicator of diagnosis and prognosis of LUAD. The combined detection of NDC80, NUF2, SPC24 and SPC25 may become a new research direction in LUAD diagnosis and a new target for tumor targeted gene therapy.

Keywords: Lung adenocarcinoma, Prognostic, NDC80 complex, Kinetochore, Tumor