Multi-Omics Analysis of MCM2 as a Promising Biomarker in Pan-Cancer

Abstract

Minichromosome maintenance 2 (MCM2) is a member of the minichromosomal maintenance family of proteins that mainly regulates DNA replication and the cell cycle and is involved in regulating cancer cell proliferation in various cancers. Previous studies have reported that MCM2 plays a pivotal role in cell proliferation and cancer development. However, few articles have systematically reported the pathogenic roles of MCM2 across cancers. Therefore, the present pan-cancer study was conducted. Various computational tools were used to investigate the MCM2 expression level, genetic mutation rate, and regulating mechanism, immune infiltration, tumor diagnosis and prognosis, therapeutic response and drug sensitivity of various cancers. The expression and function of MCM2 were examined by Western blotting and CCK-8 assays. MCM2 was significantly upregulated in almost all cancers and cancer subtypes in The Cancer Genome Atlas and was closely associated with tumor mutation burden, tumor stage, and immune therapy response. Upregulation of MCM2 expression may be correlated with a high level of alterations rate. MCM2 expression was associated with the infiltration of various immune cells and molecules and markedly associated with a poor prognosis. Western blotting and CCK-8 assays revealed that MCM2 expression was significantly upregulated in melanoma cell lines. Our results also suggested that MCM2 promotes cell proliferation in vitro by activating cell proliferation pathways such as the Akt signaling pathways. This study explored the oncogenic role of MCM2 across cancers, provided data on the underlying mechanisms of these cancers for further research and demonstrated that MCM2 may be a promising target for cancer immunotherapy.

Impaired histone inheritance promotes tumor progression

“…Recent studies have reported that abnormal expression of CAF-1 can promote tumorigenesis and drive tumor metastasis 12 – 14 . However, even though several genetic mutations in parental histone chaperones, such as MCM2 15 , 16 and POLA1 17 have been reported in a number of cancer patients, and POLE4 deficiency mice exhibit tumor predisposition 18 , whether parental histone inheritance plays a role in tumorigenesis or tumor evolution is still unclear.…”

Risk model based on minichromosome maintenance 2 using objective assessment for predicting survival of neuroblastoma

“…Several studies have recently reported that MCM2 expression could affect the immune cell infiltration. For example, an analysis of The Cancer Genome Atlas data recently revealed that MCM2 is not only significantly upregulated as a component of the tumor mutation burden, which is commonly used as a biomarker for cancer immunotherapy, 21 in advanced stages of almost all cancers but also closely associated with the infiltration of various immune cells in melanoma 22 and hepatocellular carcinoma. 23 Overall, it was expected that the interplay of MCM2 expression and tumor microenvironment critically affects tumor evolution, which subsequently impacts patient survival and immunotherapy response.…”

KNTC1 and MCM2 are the molecular targets of gallbladder cancer

“…MCM2 encodes a 904 amino acid protein with a molecular weight of 101896Da. MCM2 is a member of microchromosome maintenance protein family, regulates DNA replication and cell cycle by participating in formation of replication initiation complex [23][24][25]. Previous studies have shown that inhibition of MCM2 reduces cell viability and aggravates apoptosis in cellular models of Alzheimer's disease [26].…”