Dataset Information

Clinical Significance And Integrative Analysis Of Kinesin Family Member 18B In Lung Adenocarcinoma.

ABSTRACT: Background:Kinesin family member 18B (KIF18B) is a member of the kinesin-8 superfamily, and functions as an oncogene in human cancers. However, its expression profile and role in lung adenocarcinoma (LUAD) remain unclear. Materials and methods:We examined the expression profile of KIF18B using quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry in fresh clinical samples. Using data downloaded from the Cancer Genome Atlas database and Gene Expression Omnibus, we explored the clinical significance of KIF18B, potential mechanisms of its dysregulation and its underlying biological function in LUAD. Results:KIF18B was significantly over-expressed in LUAD tissues relative to normal tissues. High KIF18B expression was associated with smoking history, positive nodal invasion, advanced clinical stage, death status and poorer prognosis. Cox regression analyses revealed that KIF18B overexpression was an independent prognostic biomarker for poor overall survival (OS) and recurrence-free survival in LUAD. In addition, KIF18B mutation was observed in 2.2% of LUAD cases. DNA copy number variation was correlated with upregulated expression of KIF18B in LUAD tissues and cell lines. The methylation level of some KIF18B DNA CpG sites was negatively associated with its mRNA expression. KIF18B was predictively targeted by miR-125a-5p, which was downregulated in LUAD tissues, inversely correlated with KIF18B mRNA expression and significantly associated with poor OS. Furthermore, gene set enrichment analysis revealed that genes positively co-expressed with KIF18B were mainly enriched in cell cycle signaling pathways. Conclusion:Our results indicate that KIF18B is a promising prognostic biomarker for LUAD. DNA amplification, hypomethylation as well as miR-125a-5p downregulation may be involved in the mechanism of KIF18B dysregulation in LUAD. KIF18B might function as a novel oncogene through cell cycle regulation pathways in LUAD.

SUBMITTER: Zhong Y

PROVIDER: S-EPMC6842302 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Clinical Significance And Integrative Analysis Of Kinesin Family Member 18B In Lung Adenocarcinoma.

Zhong Yonglong Y Jiang Lingyu L Long Xiaomao X Zhou Yifan Y Deng Shen S Lin Hui H Li Xiangwei X

OncoTargets and therapy 20191105

<h4>Background</h4>Kinesin family member 18B (KIF18B) is a member of the kinesin-8 superfamily, and functions as an oncogene in human cancers. However, its expression profile and role in lung adenocarcinoma (LUAD) remain unclear.<h4>Materials and methods</h4>We examined the expression profile of KIF18B using quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry in fresh clinical samples. Using data downloaded from the Cancer Genome Atlas database and Gen ...[more]

PMID: 31807007

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Project description:The current study aimed to identify the potential clinical significance and molecular mechanisms of kinesin (KIF) family member genes in lung adenocarcinoma (LUAD) using genome‑wide RNA sequencing (RNA‑seq) datasets derived from The Cancer Genome Atlas (TCGA) database. Clinical parameters and RNA‑seq data of patients with LUAD from the TCGA database enabled the assessment of the clinical significance of KIF genes, while the potential mechanisms of their interactions in LUAD were investigated by gene set enrichment analysis (GSEA). A gene signature with potential prognostic value was constructed via a stepwise multivariable Cox analysis. In total, 23 KIF genes were identified to be differentially expressed genes (DEGs) between the LUAD tumor and adjacent non‑cancerous tissues. Of these, 8 differentially expressed KIF genes were strongly found to be strongly associated with the overall survival of patients with LUAD. Three of these genes were found to be able to be grouped as a potential prognostic gene signature. Patients with higher risk scores calculated using this gene signature were found to have a markedly higher risk of mortality (adjusted P=0.003; adjusted HR, 1.576; 95% CI, 1.166‑2.129). Time‑dependent receiver operating characteristic analysis indicated that this prognostic signature was able to accurately predict patient prognosis with an area under curve of 0.636, 0.643,0.665, 0.670 and 0.593 for the 1‑, 2‑, 3‑, 4‑ and 5‑year survival, respectively. This prognostic gene signature was identified as an independent risk factor for LUAD and was able to more accurately predict prognosis in comparison to other known clinical parameters, as shown via comprehensive survival analysis. GSEA enrichment revealed that that KIF14, KIF18B and KIF20A mediated basic cell physiology through the regulation of the cell cycle, DNA replication, and DNA repair biological processes and pathways. On the whole, the findings of this study identified 23 KIF genes that were DEGs between LUAD tumor and adjacent non‑cancerous tissues. In total, 8 of these genes had the potential to function as prognostic and diagnostic biomarkers in patients with LUAD.

Project description:AbstractLung adenocarcinoma (LUAD) is a lethal malignancy worldwide and a major public health concern. We explored the potential clinical significance for LUAD of ATP-binding cassette (ABC), sub-family C, consisting of ABCC1-6, 8-12, and cystic fibrosis transmembrane conductance regulator (CFTR).Five hundred LUAD patients from The Cancer Genome Atlas database were used for analysis, including differential expression and diagnostic and prognostic significance. Oncomine and MERAV databases were used to validate differential expression and diagnostic significance. A risk score model was constructed using prognosis-related ABCC members. Prognosis-related genes were further explored to correlate their expression with tumor stage progression. Interaction networks, including biological processes and metabolic pathways, were constructed using Cytoscape software and STRING website.ABCC1-3 consistently showed high expression in tumor tissues (all P ≤ 0.05). Most datasets indicated that ABCC5, 10, and 11 were highly expressed in tumor tissues whereas ABCC6, 9, and CFTR were highly expressed in nontumor tissues (all P ≤ 0.05). Diagnostic significance of ABCC3 and ABCC5 was consistently assessed and validated in three datasets (all area under the curve > 0.700) whereas ABCC6, 8, 10, 11, and CFTR were assessed in The Cancer Genome Atlas dataset and validated in one dataset (all area under the curve > 0.700). Prognostic analysis indicated that ABCC2, 6, and 8 mRNA expression was associated with survival of LUAD (all adjusted P ≤ .037). The risk score model constructed using ABCC2, 6, and 8 suggested prognostic significance for survival predictions. ABCC2 expression was associated with tumor stage, whereas ABCC6 and 8 were not. Interaction networks indicated that they were involved in establishment of localization, ion transport, plasma membrane, apical plasma membrane, adenylyl nucleotide binding, ABC transporters, ABC transporter disorders, ABC-family-protein-mediated transport, and bile secretion.Differentially expressed ABCC2 and ABCC5 might be diagnostic whereas ABCC2, 6, and 8 may be prognostic biomarkers for LUAD, possibly through ABC-family-mediated transporter disorders.

Dataset Information

Clinical Significance And Integrative Analysis Of Kinesin Family Member 18B In Lung Adenocarcinoma.

Publications

Clinical Significance And Integrative Analysis Of Kinesin Family Member 18B In Lung Adenocarcinoma.

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