Genetic variants of <scp>CHEK1</scp>, <scp>PRIM2</scp> and <scp>CDK6</scp> in the mitotic phase‐related pathway are associated with nonsmall cell lung cancer survival

Mu, Rui; Liu, Hongliang; Luo, Sheng; Patz, Edward F.; Glass, Carolyn; Li, Su; Du, Mulong; Christiani, David C.; Jin, Lei; Wei, Qingyi

doi:10.1002/ijc.33702

Cited by 16 publications

(5 citation statements)

References 45 publications

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“…As PRIM2 is intimately associated with DNA replication, the earliest step is cell cycle progression and cell division, its overexpression suggests that glioma cells are engaging in rapid and uncontrolled replication, contributing to the tumor's aggressiveness. In addition, our study is in line with the findings that high PRIM2 expression is associated with hyperactive cell cycle and aggressive disease state in other cancer types such as lung cancer (39,44).…”

Section: Figure 4 Tumor Aggressiveness Associated Changes In Gene Exp...supporting

confidence: 90%

PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients

SUN,

SHAO,

AKTER

et al. 2024

Cancer Genomics Proteomics

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Background/Aim: Gliomas are the most prevalent brain tumors with metabolic alterations playing a pivotal role in disease progression. However, the precise coordination of metabolic alterations with tumor-promoting cellular mechanisms, leading to tumor initiation, progression, and aggressiveness, resulting in poor outcomes, remains poorly understood in gliomas. Materials and Methods: We conducted a metabolism-targeted differential gene expression analysis using glioma patients' expression profiling data from The Cancer Genome Atlas (TCGA) database. In addition, pathway enrichment analysis, gene set enrichment analysis (GSEA), transcription factor prediction, network construction, and correlation analyses were performed. Survival analyses were performed in R. All results were validated using independent GEO expression datasets. Results: Metabolism-targeted analysis identified 5 hits involved in diverse metabolic processes linking them to disease aggressiveness in gliomas. Subsequently, we established that cell cycle progression and hyper-proliferation are key drivers of tumor progression and aggressiveness in gliomas. One of the identified metabolic hits, DNA primase 2 (PRIM2), a gene involved in DNA replication was found directly associated with cell cycle progression in gliomas. Furthermore, our analysis indicated that PRIM2, along with other cell cycle-related genes, is under the control of and regulated by the oncogenic MYC transcription factor in gliomas. In addition, PRIM2 expression alone is enough to predict MYC-driven cell cycle progression and is associated with tumor progression, aggressive disease state, and poor survival in glioma patients. Conclusion: Our findings highlight PRIM2 as a marker of MYC-driven cell cycle progression and hyper-proliferation, disease onset and progression, tumor aggressiveness, and poor survival in glioma patients.Cancer, a multifaceted and formidable disease, spans a wide spectrum of malignancies and continually propels the boundaries of medical research (1). Among the intricate cancer types, gliomas emerge as a particularly complex and demanding subset of tumors. These primary brain tumors originate from neuroglial stem or progenitor cells, constituting 30% of all brain tumors and over 80% of malignant brain tumors (2). With an annual incidence rate of 6.6 cases per 100,000 individuals, gliomas exhibit a notable clinical heterogeneity, encompassing both slow-growing and highly aggressive forms, resulting in diverse disease progressions and clinical outcomes (3). Gliomas have been categorized into astrocytic, oligodendroglial, or ependymal tumors based on their histological characteristics and are assigned WHO grades 1-4 accordingly which indicate different degrees of malignancy (4). Tragically, glioblastoma (GBM), the exceptionally malignant form, accounts for half of newly diagnosed gliomas, with a median patient survival duration typically ranging from 14 to 17 months. Low-grade gliomas also carry the potential to progress into more aggressive 186

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Section: Figure 4 Tumor Aggressiveness Associated Changes In Gene Exp...supporting

confidence: 90%

PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients

SUN,

SHAO,

AKTER

et al. 2024

Cancer Genomics Proteomics

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“…CD19 is an immunoglobulin expressed by B lymphocytes that plays an important role in the activity of immune cells in the lung cancer microenvironment [ 57 , 58 ]. The purpose of CHEK1 is to identify DNA damage and nonreplication, which are closely related to the occurrence of non-small cell lung cancer and drug resistance [ 59 ]. FAIM2 is involved in the process of apoptosis and can promote non-small cell lung cancer cell growth and bone metastasis by activating the Wnt/β-catenin pathway [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic correlation between specialized capillary endothelial cells and lung adenocarcinoma

Zhao,

Ding,

Han

et al. 2024

Heliyon

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“…The CHEK1 protein is a member of the Ser/Thr protein kinase family, which mediates cell cycle arrest by examining DNA replication and damage. Compared with healthy controls, the expression of the chek1 gene in lung cancer patients is relatively high [ 13 , 14 ]. The term chek1 kinase is significantly correlated with TP53 mutation, which is highly expressed in cancer tissues and negatively associated with the patient's life cycle [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Potential Key Genes and Prognostic Biomarkers of Lung Cancer Based on Bioinformatics

Cai

Xie

Liu

et al. 2023

BioMed Research International

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Objective. To analyze and identify the core genes related to the expression and prognosis of lung cancer including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) by bioinformatics technology, with the aim of providing a reference for clinical treatment. Methods. Five sets of gene chips, GSE7670, GSE151102, GSE33532, GSE43458, and GSE19804, were obtained from the Gene Expression Omnibus (GEO) database. After using GEO2R to analyze the differentially expressed genes (DEGs) between lung cancer and normal tissues online, the common DEGs of the five sets of chips were obtained using a Venn online tool and imported into the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database for Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The protein–protein interaction (PPI) network was constructed by STRING online software for further study, and the core genes were determined by Cytoscape software and KEGG pathway enrichment analysis. The clustering heat map was drawn by Excel software to verify its accuracy. In addition, we used the University of Alabama at Birmingham Cancer (UALCAN) website to analyze the expression of core genes in P53 mutation status, confirmed the expression of crucial core genes in lung cancer tissues with Gene Expression Profiling Interactive Analysis (GEPIA) and GEPIA2 online software, and evaluated their prognostic value in lung cancer patients with the Kaplan–Meier online plotter tool. Results. CHEK1, CCNB1, CCNB2, and CDK1 were selected. The expression levels of these four genes in lung cancer tissues were significantly higher than those in normal tissues. Their increased expression was negatively correlated with lung cancer patients (including LUAD and LUSC) prognosis and survival rate. Conclusion. CHEK1, CCNB1, CCNB2, and CDK1 are the critical core genes of lung cancer and are highly expressed in lung cancer. They are negatively correlated with the prognosis of lung cancer patients (including LUAD and LUSC) and closely related to the formation and prediction of lung cancer. They are valuable predictors and may be predictive biomarkers of lung cancer.

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Genetic variants of CHEK1, PRIM2 and CDK6 in the mitotic phase‐related pathway are associated with nonsmall cell lung cancer survival

Cited by 16 publications

References 45 publications

PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients

PRIM2: A Marker of MYC-driven Hyper-proliferation, Disease Progression, Tumor Aggressiveness and Poor Survival in Glioma Patients

Prognostic correlation between specialized capillary endothelial cells and lung adenocarcinoma

Identification of Potential Key Genes and Prognostic Biomarkers of Lung Cancer Based on Bioinformatics

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