Dataset Information

A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

ABSTRACT: SPC24 is over-expressed in clinical lung adenocarcinoma samples, and high level of SPC24 is associated with advanced stages of lung tumors. Knocking down SPC24 repressed cell growth and promoted apoptosis. SPC24 deficiency reduced cancer cell migration as well. E-cadherin, one of the epithelial-mesenchymal transition markers, was up-regulated in the knockdown cells, along with down-regulation of N-cadherin and Vimentin. Oncomine expression analyses further confirmed that high level of SPC24 is associated with tumors from smokers, recurrent patients, or patients with shorter survivals.To reveal the role of SPC24, an important component of kinetochore, in the tumorigenesis of lung cancer, we performed Oncomine and immunohistochemistry (IHC) analyses for SPC24 in human lung adenocarcinoma tumors. We knocked down SPC24 in two non-small cell lung cancer (NSCLC) cell lines, PC9 and A549, by siRNA and evaluated cell proliferation, apoptosis, and migration in the SPC24-deficient cells. Using a mouse xenograft model, we compared in vivo tumor growth of the knockdown and control cells. We further performed multiple Oncomine expression analyses for SPC24 in various lung cancer datasets with important clinical characteristics and risk factors, including survival, recurrence, and smoking status.SPC24 is a novel oncogene of lung cancer, and can serve as a promising prognostic biomarker to differentiate lung tumors that have various clinicopathological characteristics. The findings of the current study will benefit the diagnosis, management, and targeted therapy of lung cancer.

SUBMITTER: Zhou J

PROVIDER: S-EPMC5630346 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

Zhou Juan J Yu Yang Y Pei Yunfeng Y Cao Chunping C Ding Chen C Wang Duping D Sun Li L Niu Guoping G

Oncotarget 20170704 39

<h4>Results</h4>SPC24 is over-expressed in clinical lung adenocarcinoma samples, and high level of <i>SPC24</i> is associated with advanced stages of lung tumors. Knocking down SPC24 repressed cell growth and promoted apoptosis. SPC24 deficiency reduced cancer cell migration as well. E-cadherin, one of the epithelial-mesenchymal transition markers, was up-regulated in the knockdown cells, along with down-regulation of N-cadherin and Vimentin. Oncomine expression analyses further confirmed that h ...[more]

PMID: 29029446

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Project description:BackgroundTo research the correlation between the prognosis of patients suffering from lung adenocarcinoma (LUAD) and methyltransferase like 7B (METTL7B) expression.MethodsThe Cancer Genome Atlas (TCGA) database was utilized to verify METTL7B expression, and The Human Protein Atlas database was utilized to verify METTL7B expression at the tissue level. The relationship between METTL7B and LUAD prognostic data was then analyzed using the KM-plotter database. The correlation between METTL7B expression and immune cells was demonstrated through the TIMER database. For exploring the possible mechanism of action, gene set enrichment analysis (GSEA) was performed. Finally, the role of METTL7B in the adverse biological events of LUAD was further explored by in vitro experiments such as proliferation and invasion assays.ResultsAs per the TCGA database, METTL7B expression was increased in cancerous tissues compared with paracancerous tissues, and it was mostly located in the cytoplasm. Patients suffering from LUAD who had low METTL7B expression had a relatively better overall survival (OS) and disease-specific survival (DSS) according to the Kaplan-Meier-plotter (KM-plotter) database. METTL7B expression was significantly associated with immune cell infiltration in LUAD patients, as shown by correlation analysis. GSEA revealed that METTL7B may affect the physiological events of LUAD by playing a part in cell cycle regulation. In vitro cytological experiments demonstrated that METTL7B can markedly affect the metastasis of LUAD cells.ConclusionsThe reduction of METTL7B expression can prolong OS and DSS in LUAD patients. It may be utilized as a novel predictive biomarker of LUAD, and may be associated with immune infiltration of LUAD. Interfering with METTL7B expression can significantly cause inhibition of LUAD by modulating the ability of cells to proliferate and migrate. These results point to a possible target for developing anti-cancer therapies against LUAD.

Project description:Most prostate cancer (PCa) cases remain indolent with a relatively good prognosis. However, bone metastasis of PCa can quickly worsen prognoses and lead to mortality. Metastasis-free survival (MFS), a strong surrogate for overall survival, is widely used in PCa prognosis research. The present study identified molecules that affect bone MFS in PCa, with clinical validation. Three datasets (GSE32269, GSE74367 and GSE77930) were downloaded from the Gene Expression Omnibus database. Hub genes most relevant to clinical traits (bone metastasis-associated morbidity) were identified by weighted gene co-expression network analysis (WGCNA) and subjected to logistic regression analysis. Patient samples were obtained between January 2014 and December 2016, with a clinically annotated follow-up in December 2021. Clinical data and follow-up information for 60 patients with PCa were used in MFS analysis. Tumor samples were retrieved, and immunohistochemistry was performed to detect vascular endothelial growth factor (VEGF). The prognostic potential of the two molecules was assessed using Cox proportional hazards regression analysis. A total of 16 gene modules were obtained via WGCNA, and the tan module, containing 147 genes, was most closely linked to bone metastasis. In total, 877 differentially expressed genes (DEGs) were detected. The DEG-tan module intersection yielded seven hub genes [BUB1, kinesin family member (KIF)2C, RACGAP1, CENPE, KIF11, TTK and KIF20A]. Using univariate and multivariate logistic regression analyses for independent risk factors of bone metastasis, KIF11 and VEGF were found to be significantly associated with a higher T stage, prostate-specific antigen level and Gleason score. In addition, KIF11 and VEGF expression levels were positively correlated (P<0.001). Using univariate Cox analysis, KIF11 and VEGF were found to exhibit a significant association with poor MFS (P<0.05). However, only KIF11 was significantly associated with MFS upon multivariate analysis (P=0.007; hazard ratio, 2.776; 95% confidence interval, 1.315-5.859). Markers of bone metastasis in PCa were identified. Overall, KIF11 is an independent indicator that can predict bone metastasis for patients with PCa, which could be used to guide clinical practice.

Dataset Information

A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

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A potential prognostic biomarker SPC24 promotes tumorigenesis and metastasis in lung cancer.

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