Overexpression of MCM6 predicts poor survival in patients with glioma

Cai, Hong‐Qing; Zhang, Cheng; Zhang, Haipeng; Wang, Pengfei; Zhang, Yu; Hao, Jia‐Jie; Wang, Ming-Rong; Wan, Jinghai

doi:10.1016/j.humpath.2018.04.024

Cited by 40 publications

(39 citation statements)

References 24 publications

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“…The minichromosome maintenance protein (MCM) family is implicated in the control of eukaryotic genome replication and proves to be useful markers for tumor proliferation [24]. Several studies demonstrated overexpression of MCM6 also predicts poor survival in patients with several types of cancer, including HCC [31][32][33][34]. Future studies should attempt to clarify the underlying mechanism of GTSE1 together with minichromosome-related protein-mediated DNA replication and cancer prognosis.…”

Section: Discussionmentioning

confidence: 99%

GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer

Zheng

Shi

et al. 2019

Analytical Cellular Pathology

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GTSE1 is well correlated with tumor progression; however, little is known regarding its role in liver cancer prognosis. By analyzing the hepatocellular carcinoma (HCC) datasets in GEO and TCGA databases, we showed that high expression of GTSE1 was correlated with advanced pathologic stage and poor prognosis of HCC patients. To investigate underlying molecular mechanism, we generated GTSE1 knockdown HCC cell line and explored the effects of GTSE1 deficiency in cell growth. Between GTSE1 knockdown and wild-type HCC cells, we identified 979 differentially expressed genes (520 downregulated and 459 upregulated genes) in the analysis of microarray-based gene expression profiling. Functional enrichment analysis of DEGs suggested that S phase was dysregulated without GTSE1 expression, which was further verified from flow cytometry analysis. Moreover, three other DEGs: CDC20, PCNA, and MCM6, were also found contributing to GTSE1-related cell cycle arrest and to be associated with poor overall survival of HCC patients. In conclusion, GTSE1, together with CDC20, PCNA, and MCM6, may synergistically promote adverse prognosis in HCC by activating cell cycle. Genes like GTSE1, CDC20, PCNA, and MCM6 may be promising prognostic molecular biomarkers in liver cancer.

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Section: Discussionmentioning

confidence: 99%

GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer

Zheng

Shi

et al. 2019

Analytical Cellular Pathology

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“…MCM proteins are suggested to be closely related to cancer development as well. Overexpression of MCMs has been detected in various cancer tissues and carcinoma cell lines including lung squamous cell carcinoma [26], renal cell carcinoma [27], prostate cancer [28], breast cancer [29], gastrointestinal tract tumors [30][31][32], brain tumors [33,34], and lymphomas [35,36]. Studies have also shown the links between critical clinicopathological characteristics and upregulated MCMs in some cancers [37,38].…”

Section: Mcms and Cancermentioning

confidence: 99%

“…[ 3 Analytical Cellular Pathology multivariate survival analyses with Cox's regression model present evidence for independent prognostic roles of MCM2 in LUSC prognosis [26], MCM6 in glioma [33], MCM5 in lung squamous cell carcinoma [70], and MCM8 in pancreatic cancer [31].…”

Section: Mcm6mentioning

confidence: 99%

“…Other Molecules In addition to geminin and GINS, many other molecules may work in combination with MCMs in prognostic prediction. IDH1 mutation, a classical biomarker in glioma, was reported to combinate MCM6 overexpressions to improve the prediction of the prognosis in glioblastomas [33]. MCM4 and MCM7 expressions were significantly associated with Ki-67, Bmi1, and cyclin E expression in esophageal carcinoma prognosis [47].…”

Section: Interactions With Other Molecules Gemininmentioning

confidence: 99%

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MCMs in Cancer: Prognostic Potential and Mechanisms

Wang

Shi

et al. 2020

Analytical Cellular Pathology

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Enabling replicative immortality and uncontrolled cell cycle are hallmarks of cancer cells. Minichromosome maintenance proteins (MCMs) exhibit helicase activity in replication initiation and play vital roles in controlling replication times within a cell cycle. Overexpressed MCMs are detected in various cancerous tissues and cancer cell lines. Previous studies have proposed MCMs as promising proliferation markers in cancers, while the prognostic values remain controversial and the underlying mechanisms remain unascertained. This review provides an overview of the significant findings regarding the cellular and tumorigenic functions of the MCM family. Besides, current evidence of the prognostic roles of MCMs is retrospectively reviewed. This work also offers insight into the mechanisms of MCMs prompting carcinogenesis and adverse prognosis, providing information for future research. Finally, MCMs in liver cancer are specifically discussed, and future perspectives are provided.

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“…In adamantinomatous craniopharyngiomas, MCM6 correlated with a higher risk of long-term recurrence (48). In gliomas, especially in glioblastomas of the Chinese Cancer Genome Atlas (CCGA), MCM6 mRNA overexpression was also reported to be correlated with poor overall survival (9).…”

Section: Introductionmentioning

confidence: 99%

Ki‐67 and MCM6 labeling indices are correlated with overall survival in anaplastic oligodendroglioma, IDH1‐mutant and 1p/19q‐codeleted: a multicenter study from the French POLA network

et al. 2019

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Anaplastic oligodendroglioma (AO), IDH-mutant and 1p/19q codeleted (IDHmut+/ 1p19qcodel), is a high-grade glioma with only limited prognostic markers. The primary objective of this study was to evaluate, by immunohistochemistry, the prognostic value of two proliferation markers, MCM6 and Ki-67, in a large series of IDHmut+/1p19qcodel AO included in the POLA ("Prise en charge des Oligodendrogliomes Anaplasiques") French national multicenter network. We additionally examined the transcriptome obtained from this series to understand the functional pathways dysregulated with the mRNA overexpression of these two markers. The labeling indices (LI) of MCM6 and Ki-67 were obtained via computer-assisted color image analyses on immunostained AO tissues of the cohort (n = 220). Furthermore, a subgroup of AO (n = 68/220) was used to perform transcriptomic analyses. A high LI of either MCM6 (≥50%) or Ki-67 (≥15%) correlated with shorter overall survival, both in univariate (P = 0.013 and P = 0.004, respectively) and multivariate analyses (P = 0.027; multivariate Cox model including age, mitotic index, MCM6 and Ki-67). MCM6 and Ki-67 LI also correlated with overall survival in an additional retrospective cohort of 30 grade II IDHmut+/1p19qcodel oligodendrogliomas. The prognostic value of MCM6 mRNA level was confirmed in The Cancer Genome Atlas (TCGA) IDHmut+/1p19qcodel gliomas. The transcriptomic approach revealed that high transcriptional expressions of MCM6 and MKI67 were both linked positively with cell cycle progression, DNA replication, mitosis, pro-neural phenotype as well as neurogenesis, and negatively with microglial cell activation, immune response, positive regulation of myelination, oligodendrocyte development, beta-amyloid binding and postsynaptic specialization. In conclusion, the overexpression of MCM6 and/or Ki-67 is independently associated to shorter overall survival in IDHmut+/1p19qcodel AO. These two easy-to-use and cost-effective markers could thus be used concurrently in routine pathology practice. Additionally, the transcriptomic analyses showed that AO with high proliferation index have down-regulated immune response and lower microglial cells activation, and bears pro-neural phenotype.

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Overexpression of MCM6 predicts poor survival in patients with glioma

Cited by 40 publications

References 24 publications

GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer

GTSE1, CDC20, PCNA, and MCM6 Synergistically Affect Regulations in Cell Cycle and Indicate Poor Prognosis in Liver Cancer

MCMs in Cancer: Prognostic Potential and Mechanisms

Ki‐67 and MCM6 labeling indices are correlated with overall survival in anaplastic oligodendroglioma, IDH1‐mutant and 1p/19q‐codeleted: a multicenter study from the French POLA network

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