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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation
Junneng Zhang1, Huanzong Zhang1, Yinghui Wang1
1Laboratory Medicine Department, The Fifth Hospital of Xiamen, Xiamen, China.
Background:
Clear cell renal cell carcinoma (ccRCC) accounts for 60-70% of renal cell carcinoma (RCC) cases. Finding more therapeutic targets for advanced ccRCC is an urgent mission. The minichromosome maintenance proteins 2-7 (MCM2-7) protein forms a stable heterohexamer and plays an important role in DNA replication in eukaryotic cells. In the study, we provide a comprehensive study of MCM2-7 genes expression and their potential roles in ccRCC.
Methods:
The expression and prognosis of the MCM2-7 genes in ccRCC were analyzed using data from TCGA, GEO and ArrayExpress. MCM2-7 related genes were identified by weighted co-expression network analysis (WGCNA) and Metascape. CancerSEA and GSEA were used to analyze the function of MCM2-7 genes in ccRCC. The gene effect scores (CERES) of MCM2-7, which reflects carcinogenic or tumor suppressor, were obtained from DepMap. We used clinical and expression data of MCM2-7 from the TCGA dataset and the LASSO Cox regression analysis to develop a risk score to predict survival of patients with ccRCC. The correlations between risk score and other clinical indicators such as gender, age and stage were also analyzed. Further validation of this risk score was engaged in another cohort, E-MTAB-1980 from the ArrayExpress dataset.
Results:
The mRNA and protein expression of MCM2-7 were increased in ccRCC compared with normal tissues. High MCM2, MCM4, MCM6 and MCM7 expression were associated with a poor prognosis of ccRCC patients. Functional enrichment analysis revealed that MCM2-7 might influence the progress of ccRCC by regulating the cell cycle. Knockdown of MCM7 can inhibit the proliferation of ccRCC cells. A two-gene risk score including MCM4 and MCM6 can predict overall survival (OS) of ccRCC patients. The risk score was successfully verified by further using Arrayexpress cohort.
Conclusion:
We analyze MCM2-7 mRNA and protein levels in ccRCC. MCM7 is determined to promote tumor proliferation. Meanwhile, our study has determined a risk score model composed of MCM2-7 can predict the prognosis of ccRCC patients, which may help future treatment strategies.
Insights
Minichromosome maintenance proteins 2-7 (MCM2-7) are upregulated in clear cell renal cell carcinoma (ccRCC). A risk score based on MCM4 and MCM6 predicts patient survival, offering potential therapeutic insights for advanced ccRCC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer.
- Identifying novel therapeutic targets for advanced ccRCC is a critical unmet need.
- Minichromosome maintenance proteins 2-7 (MCM2-7) are essential for DNA replication and are implicated in cancer progression.
Purpose of the Study:
- To comprehensively investigate the expression and prognostic significance of MCM2-7 genes in ccRCC.
- To explore the functional roles of MCM2-7 in ccRCC pathogenesis.
- To develop and validate a predictive risk score for ccRCC patient survival.
Main Methods:
- Analysis of MCM2-7 gene expression and survival data from TCGA, GEO, and ArrayExpress databases.
- Weighted gene co-expression network analysis (WGCNA) and Metascape for identifying MCM2-7 related genes.
- CancerSEA and Gene Set Enrichment Analysis (GSEA) for functional enrichment.
- LASSO Cox regression analysis to develop a prognostic risk score.
- Validation of the risk score in an independent cohort.
Main Results:
- MCM2-7 mRNA and protein levels are significantly elevated in ccRCC tissues compared to normal tissues.
- High expression of MCM2, MCM4, MCM6, and MCM7 correlates with poorer prognosis in ccRCC patients.
- Functional analysis suggests MCM2-7 regulates the cell cycle in ccRCC progression.
- Knockdown of MCM7 inhibits ccRCC cell proliferation.
- A two-gene risk score (MCM4 and MCM6) effectively predicts overall survival (OS) in ccRCC patients, validated in an independent cohort.
Conclusions:
- MCM2-7 genes are upregulated in ccRCC, with MCM7 promoting tumor proliferation.
- A novel MCM2-7-based risk score accurately predicts ccRCC patient prognosis.
- This risk score holds potential for guiding future treatment strategies in ccRCC.
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