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.

Frontiers in Oncology
|January 7, 2022
PubMed
Abstract

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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