Prognostic relevance of topoisomerase II α and minichromosome maintenance protein 6 expression in colorectal cancer

Hendricks, Alexander; Gieseler, Frank; Nazzal, Saleh; Bräsen, Jan Hinrich; Lucius, Ralph; Sipos, Bence; Claasen, Julia; Becker, T; Hinz, Sebastian; Burmeister, Greta; Schafmayer, Clemens; Schrader, Carsten

doi:10.1186/s12885-019-5631-3

Cited by 15 publications

(8 citation statements)

References 30 publications

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“…The encoded product of MCM6 is a key protein for DNA replication and is involved in the regulation of the cell cycle (Lei, 2005). MCM6 is highly expressed in colon cancer tissues (Hendricks et al, 2019). Huang et al (2018) showed that the suppression of MCM6 in colon cancer cells could inhibit the foci-forming and chromatin localization of RAD51 recombinase (RAD51), a protein essential for DNA damage recovery.…”

Section: Featurementioning

confidence: 99%

Bioinformatics Analysis of Prognostic miRNA Signature and Potential Critical Genes in Colon Cancer

et al. 2020

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This study aims to lay a foundation for studying the regulation of microRNAs (miRNAs) in colon cancer by applying bioinformatics methods to identify miRNAs and their potential critical target genes associated with colon cancer and prognosis. Data of differentially expressed miRNAs (DEMs) and genes (DEGs) downloaded from two independent databases (TCGA and GEO) and analyzed by R software resulted in 472 DEMs and 565 DEGs in colon cancers, respectively. Next, we developed an 8-miRNA (hsa-mir-6854, hsa-mir-4437, hsa-mir-216a, hsa-mir-3677, hsa-mir-887, hsa-mir-4999, hsa-mir-34b, and hsa-mir-3189) prognostic signature for patients with colon cancer by Cox proportional hazards regression analysis. To predict the target genes of these miRNAs, we used TargetScan and miRDB. The intersection of DEGs with the target genes predicted for these eight miRNAs retrieved 112 consensus genes. GO and KEGG pathway enrichment analyses showed these 112 genes were mainly involved in protein binding, one-carbon metabolic process, nitrogen metabolism, proteoglycans in cancer, and chemokine signaling pathways. The protein-protein interaction network of the consensus genes, constructed using the STRING database and imported into Cytoscape, identified 14 critical genes in the pathogenesis of colon cancer (CEP55,

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Section: Featurementioning

confidence: 99%

Bioinformatics Analysis of Prognostic miRNA Signature and Potential Critical Genes in Colon Cancer

et al. 2020

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“…It functions by unwinding the two DNA spiral strands [9] and by promoting G1/S transition [10]. Many studies have shown that the level of expression of MCM6, basing on mRNA detection or immunohistochemistry, was correlated with clinical outcome, e.g., in gliomas, renal cell carcinoma, endometrial adenocarcinoma, lung cancer, osteosarcoma, pheochromocytoma, neuroblastoma, and meningioma [4,[10][11][12][13][14][15][16][17][18][19][20]. Our previous evidence singled out MCM6 as an efficient marker by virtue of its dominant presence in proliferating cells that resulted in striking clear-cut differences in MCM6 labeling index (LI) of the indolent vs. the recurrent meningiomas, with a high reproducibility [4].…”

Section: Introductionmentioning

confidence: 99%

A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals

Gauchotte

Bédel

Lardenois

et al. 2023

Cancers

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The aim of this study was to evaluate the prognostic value of MCM6, in comparison with Ki-67, in two series of grade 1 and 2 meningiomas, and to evaluate its correlation with methylation classes. The first cohort included 100 benign (grade 1, World Health Organization 2021) meningiomas, and the second 69 atypical meningiomas (grade 2). Immunohistochemical Ki-67 and MCM6 labeling indices (LI) were evaluated independently by two observers. Among the atypical meningiomas, 33 cases were also studied by genome-wide DNA methylation. In grade 2 meningiomas, but not grade 1, both Ki-67 and MCM6 LIs were correlated with PFS (p = 0.004 and p = 0.005, respectively; Cox univariate analyses). Additionally, MCM6 was correlated with overall survival only in univariate analysis. In a multivariate model, including mitotic index, Ki-67, MCM6, age, sex, and the quality of surgical resection, only MCM6 was correlated with PFS (p = 0.046). Additionally, we found a significant correlation between PTEN loss and high MCM6 or Ki-67 LIs. Although no correlation was found with the methylation classes and subtypes returned by the meningioma algorithm MNGv2.4., MCM6 LI was significantly correlated with the methylation of 2 MCM6 gene body loci. In conclusion, MCM6 is a relevant prognostic marker in atypical meningiomas. This reproducible and easy-to-use marker allows the identification of a highly aggressive subtype of proliferative meningiomas, characterized notably by frequent PTEN losses, which was previously reported to be sensitive to histone deacetylase inhibitors.

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“…A precise and robust gene signature can significantly aid in the clinical identification of disease [ 11 ]. Bioinformatics methods have been widely used to analyze high-throughput sequencing data and microarray data for the prediction of disease-related genes, such as renal cell carcinoma [ 12 ], triple-negative breast cancer [ 13 ], and colorectal cancer [ 14 ]. However, few of these studies examined the effect of nutritional deficiency in the tumor microenvironment on tumor prognosis, which was very important in tumor progression.…”

Section: Introductionmentioning

confidence: 99%

[Retracted] Identification of a 5‐Nutrient Stress‐Sensitive Gene Signature to Predict Survival for Colorectal Cancer

Xiong

Xiong²,

Xing

et al. 2022

BioMed Research International

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Background. The high heterogeneity and the complexity of the tumor microenvironment of colorectal cancer (CRC) have enhanced the difficulty of prognosis prediction based on conventional clinical indicators. Recent studies revealed that tumor cells could overcome various nutritional deficiencies by gene regulation and metabolic remodeling. However, whether differentially expressed genes (DEGs) in CRC cells under kinds of nutrient deficiency could be used to predict prognosis remained unveiled. Methods. Three datasets (GSE70976, GSE13548, and GSE116087), in which colon cancer cells were, respectively, cultured in serum-free, glucose-free, or glutamine-free medium, were included to delineate the profiles of gene expression by nutrient stress. DEGs were figured out in three datasets, and gene functional analysis was performed. Survival analyses and Cox proportional hazards model were then used to identify nutrient stress sensitive genes in CRC datasets (GSE39582 and TCGA COAD). Then, a 5-gene signature was constructed and the risk scores were also calculated. Survival analyses, cox analyses, and nomogram were applied to predict the prognosis of patients with colorectal cancer. The effectiveness of the risk model was also tested. Results. A total of 48 genes were found to be dysregulated in serum, glucose, or glutamine-deprived CRC cells, which were mainly enriched in cell cycle and endoplasmic reticulum stress pathways. After further analyses, 5 genes, MCM5, MCM6, CDCA2, GINS2, and SPC25, were identified to be differentially expressed in CRC and be related to prognosis of in CRC datasets. We used the above nutrient stress-sensitive genes to construct a risk scoring model. CRC samples in the datasets were divided into low-risk and high-risk groups. Data showed that higher risk scores were associated with better outcomes and risk scores decreased significantly with tumor procession. Moreover, the risk score could be used to predict the probability of survival based on nomogram. Conclusions. The 5-nutrient stress-sensitive gene signature could act as an independent biomarker for survival prediction of CRC patients.

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Prognostic relevance of topoisomerase II α and minichromosome maintenance protein 6 expression in colorectal cancer

Cited by 15 publications

References 30 publications

Bioinformatics Analysis of Prognostic miRNA Signature and Potential Critical Genes in Colon Cancer

Bioinformatics Analysis of Prognostic miRNA Signature and Potential Critical Genes in Colon Cancer

A High MCM6 Proliferative Index in Atypical Meningioma Is Associated with Shorter Progression Free and Overall Survivals

[Retracted] Identification of a 5‐Nutrient Stress‐Sensitive Gene Signature to Predict Survival for Colorectal Cancer

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