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

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.

Identification of candidate genes and prognostic value analysis in patients with PDL1-positive and PDL1-negative lung adenocarcinoma

“…Several hub genes, such as BUB1B, CDC45, BUB1, TTK, TOP2A, MCM2, NDC80, and DTL, have been reported to be associated with poor prognosis in patients with lung adenocarcinoma (Hayama et al, 2006;He et al, 2019;Liu et al, 2017;Perez-Pea et al, 2017;Song et al, 2018;Sun et al, 2020). Our findings corroborate these results.…”

The Clinical Significance and Potential Molecular Mechanisms of Synaptojanin 2 in Lung Adenocarcinoma

“…KIF20A also has been detected as being overexpressed in numerous types of human malignancies, including LUAD, and its overexpression can stimulate LUAD cells' proliferation [48]. Matching our results, Sun et al [49] also reported that NDC80 expression was strikingly elevated in LUAD and related to prognosis. Interestingly, relevant studies about TPX2, MELK, KIF2C, and KIF11 also have been reported in LUAD, and they are all implicated with the progression and poor prognosis of LUAD [50][51][52][53].…”

NUF2 Correlates with&nbsp;Poor Prognosis in Non-Small Cell Lung Cancer: A Systematic Multi-Omics Analysis

“…NUF2 is also an oncogene that is over-expressed on several cancers [5,20], including lung adenocarcinoma. Comparing with previous study, the NUF2 expression in multiple databases was signi cantly higher than in normal tissues, and also signi cantly higher in LUAD and LUSC [7].…”

“…The nuclear division cycle 80(NDC80) complex is a heterotetrameric protein complex, and NUF2, as an important part of the NDC80 complex, is essential for kinetochore-microtubule attachment and chromosome separation [3]. Previous evidence demonstrated that NUF2 plays as a prognostic biomarker and therapeutic target in hepatocellular carcinoma, breast cancer and oral cancer [4][5][6], and NDC80 complex gene might be an early indicator of diagnosis and prognosis of lung adenocarcinoma [7]. These studies have shown that NUF2 might be a candidate biomarker and therapeutic target in cancer with great potential, but the role of the NUF2 gene in NSCLC has not been systematically explored in multiple aspects.…”