SPC25 upregulation increases cancer stem cell properties in non-small cell lung adenocarcinoma cells and independently predicts poor survival

Chen, Jingxia; Chen, Hongfen; Yang, Hanbing; Dai, Huizhen

doi:10.1016/j.biopha.2018.02.015

Cited by 39 publications

(52 citation statements)

References 22 publications

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“…SPC25 upregulation can increase cancer stem cell properties in lung adenocarcinoma and independently predict poor survival in patients with lung adenocarcinoma. The knockdown of SPC25 impaired the cancer stem cell properties in lung adenocarcinoma (Chen et al, 2018a). A recent study also revealed that SPC25 knockdown promoted the apoptosis of prostate cancer cells (Cui et al, 2018).…”

Section: Discussionmentioning

confidence: 94%

Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma

Yang

Sun

Song

et al. 2020

PeerJ

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Background Spindle pole body component 25 (SPC25) plays a vital role in many cellular processes, such as tumorigenesis. However, the clinical significance of SPC25 in hepatocellular carcinoma (HCC) has not been investigated. This study aimed to explore the expression patterns of SPC25 in HCC and non-neoplastic tissues and to investigate the diagnostic and prognostic values of SPC25. Method The expression of SPC25 was examined in 374 HCC issues and 50 non-neoplastic tissues from The Cancer Genome Atlas (TCGA) cohort. The diagnostic and prognostic values of SPC25 were analyzed via receiver operating characteristic (ROC) curve and survival analyses, respectively. Univariate and multivariate Cox regression analyses were used to identify the prognostic factors and to establish a nomogram. The diagnostic and prognostic values were further validated in an external cohort from the International Cancer Genome Consortium (ICGC) database. Results The expression of SPC25 in HCC tissues was significantly higher than that in normal tissues in both cohorts (all P < 0.001). The ROC curve analysis indicated that SPC25 expression has high diagnostic value in HCC with area under the curve (AUC) value of 0.969 (95% confidence interval [CI] [0.948–0.984]) and 0.945 (95% CI [0.920–0.965]) for TCGA and ICGC cohorts, respectively. Patients with HCC exhibiting high SPC25 expression were associated with worse prognosis than those exhibiting low SPC25 expression in both cohorts (all P < 0.001). SPC25 was independently associated with overall survival in both cohorts (all P < 0.001). The concordance indices of the nomogram for predicting overall survival in TCGA and ICGC cohorts were 0.647 and 0.805, respectively, which were higher than those of the American Joint Committee on Cancer (AJCC) staging system. Conclusion SPC25 was upregulated in HCC and independently predicted poor overall survival of patients with HCC. Therefore, SPC25 is an effective diagnostic and prognostic biomarker for HCC. An SPC25-based nomogram was more accurate and useful than the AJCC staging system to predict prognosis of HCC.

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Section: Discussionmentioning

confidence: 94%

Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma

Yang

Sun

Song

et al. 2020

PeerJ

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“…Here, all of the mutual interactors of Survivin exhibited significant regulation, which led to a reduced expression of these molecules in Pirfenidone treated A549 cells ( Figure 4B). Furthermore, Survivin/BIRC5 interacted closely with molecules ( Figure 4C) which were shown to regulate stem cell properties in lung adenocarcinomas (SPC25) (28), influence radiosensitivity in lung cancer (AURKA) (29), or mediate anti-EGFR therapy in NSCLC (AURKB) (30). Interestingly, a majority of Survivin interacting molecules that were found to be significantly regulated by Pirfenidone are also associated with the mitotic spindle (MAD2L1, BUB1, BUB1B, BUB3, CDC20) and were shown to be increased in human breast cancer (31).…”

Section: Pirfenidone Down-regulated Survivin Affected Apoptotic Signmentioning

confidence: 99%

The Multi-Modal Effect of the Anti-fibrotic Drug Pirfenidone on NSCLC

et al. 2020

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Although immune checkpoint and targeted therapies offer remarkable benefits for lung cancer treatment, some patients do not qualify for these regimens or do not exhibit consistent benefit. Provided that lung cancer appears to be driven by transforming growth factor beta signaling, we investigated the single drug potency of Pirfenidone, an approved drug for the treatment of lung fibrosis. Five human lung cancer cell lines and one murine line were investigated for transforming growth factor beta inhibition via Pirfenidone by using flow cytometry, In-Cell western analysis, proliferation assays as well as comprehensive analyses of the transcriptome with subsequent bioinformatics analysis. Overall, Pirfenidone induced cell cycle arrest, down-regulated SMAD expression and reduced proliferation in lung cancer. Furthermore, cell stress pathways and pro-apoptotic signaling may be mediated by reduced expression of Survivin. A murine subcutaneous model was used to assess the in vivo drug efficacy of Pirfenidone and showed reduced tumor growth and increased infiltration of T cells and NK cells. This data warrant further clinical evaluation of Pirfenidone with advanced non-small cell lung cancer. The observed in vitro and in vivo effects point to a substantial benefit for using Pirfenidone to reactivate the local immune response and possible application in conjunction with current immunotherapies.

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“…Factors responsible for lung cancer include genetic and signaling pathway abnormalities. Hence, it is important to understand the associated genes and their mechanisms in the development of lung cancer [3,7,8]. The nuclear division cycle 80 (NDC80) complexes consisting of NDC80, NUF2, SPC24, and SPC25 form a heterotetrameric protein complex located in the outer layer of the kinetochore and link the kinetochore to microtubules during mitosis [9][10][11].…”

Section: Ivyspringmentioning

confidence: 99%

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

Sun¹,

Wang²,

Gao³

et al. 2020

J. Cancer

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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.

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SPC25 upregulation increases cancer stem cell properties in non-small cell lung adenocarcinoma cells and independently predicts poor survival

Cited by 39 publications

References 22 publications

Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma

Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma

The Multi-Modal Effect of the Anti-fibrotic Drug Pirfenidone on NSCLC

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

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