Diagnostic and prognostic value of MCM3 and its interacting proteins in hepatocellular carcinoma

Li, Hongtao; Wei, Bing; Li, Zhouquan; Wang, Xiao; Jia, Wenxian; Xu, Yijuan; Liu, Jiayi; Shao, Meng-Nan; Chen, Suixia; Mo, Nanfang; Zhao, Dong; Zuo, Wenpu; Qin, Jian; Li, Ping; Zhang, Qinle; Yang, Xiaoli

doi:10.3892/ol.2020.12171

Cited by 14 publications

(21 citation statements)

References 47 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These results indicate that MCM3 may be related to tumor proliferation, migration, and invasion. Increased level of MCM3 has also been observed in liver cancer, salivary gland tumors, prostate cancer, melanoma, and cervical squamous cell carcinoma (23,(25)(26)(27)(28). These studies indicate that MCM3 may be a potential proliferation marker for the diagnosis of certain tumors.…”

Section: Discussionmentioning

confidence: 67%

MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation

Zhang¹,

Zhang²,

Wang³

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

BackgroundClear 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.MethodsThe 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.ResultsThe 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.ConclusionWe 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.

show abstract

Section: Discussionmentioning

confidence: 67%

MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation

Zhang¹,

Zhang²,

Wang³

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…MCM2 belongs to the minichromosome maintenance (MCM) protein complex which is involved in the initiation of DNA replication and DNA unwinding [ 42 ]. MCM2 is a subunit/component of the hexameric protein complex that consists of MCM2-7 and directly interacts with MCM5 [ 63 ]. In vitro studies indicate that MCM2 silencing inhibits cell proliferation by affecting the G1/S transition and conversely the overexpression of MCM2 promotes cell proliferation in lung cancer cells [ 64 ]; moreover, MCM2 knockdown inhibits cell migration in lung cancer cells.…”

Section: Discussionmentioning

confidence: 99%

A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

Bedon

Mossenta

et al. 2021

IJMS

View full text Add to dashboard Cite

Although extensive advancements have been made in treatment against hepatocellular carcinoma (HCC), the prognosis of HCC patients remains unsatisfied. It is now clearly established that extensive epigenetic changes act as a driver in human tumors. This study exploits HCC epigenetic deregulation to define a novel prognostic model for monitoring the progression of HCC. We analyzed the genome-wide DNA methylation profile of 374 primary tumor specimens using the Illumina 450 K array data from The Cancer Genome Atlas. We initially used a novel combination of Machine Learning algorithms (Recursive Features Selection, Boruta) to capture early tumor progression features. The subsets of probes obtained were used to train and validate Random Forest models to predict a Progression Free Survival greater or less than 6 months. The model based on 34 epigenetic probes showed the best performance, scoring 0.80 accuracy and 0.51 Matthews Correlation Coefficient on testset. Then, we generated and validated a progression signature based on 4 methylation probes capable of stratifying HCC patients at high and low risk of progression. Survival analysis showed that high risk patients are characterized by a poorer progression free survival compared to low risk patients. Moreover, decision curve analysis confirmed the strength of this predictive tool over conventional clinical parameters. Functional enrichment analysis highlighted that high risk patients differentiated themselves by the upregulation of proliferative pathways. Ultimately, we propose the oncogenic MCM2 gene as a methylation-driven gene of which the representative epigenetic markers could serve both as predictive and prognostic markers. Briefly, our work provides several potential HCC progression epigenetic biomarkers as well as a new signature that may enhance patients surveillance and advances in personalized treatment.

show abstract

“…Additionally, a series of recent studies correlated MCM expression with the development of hepatocellular carcinoma [92][93][94][95]. The MCM proteins are not highly expressed in somatic cells that have withdrawn from the cell cycle, making MCM proteins an ideal diagnostic marker for cancer and promising targets for the development of anti-cancer drugs [90,96].…”

Section: (Minichromosome Maintenance Complex)mentioning

confidence: 99%

OB-Folds and Genome Maintenance: Targeting Protein–DNA Interactions for Cancer Therapy

Par

Vaides

VanderVere-Carozza

et al. 2021

Cancers

View full text Add to dashboard Cite

Genome stability and maintenance pathways along with their requisite proteins are critical for the accurate duplication of genetic material, mutation avoidance, and suppression of human diseases including cancer. Many of these proteins participate in these pathways by binding directly to DNA, and a subset employ oligonucleotide/oligosaccharide binding folds (OB-fold) to facilitate the protein–DNA interactions. OB-fold motifs allow for sequence independent binding to single-stranded DNA (ssDNA) and can serve to position specific proteins at specific DNA structures and then, via protein–protein interaction motifs, assemble the machinery to catalyze the replication, repair, or recombination of DNA. This review provides an overview of the OB-fold structural organization of some of the most relevant OB-fold containing proteins for oncology and drug discovery. We discuss their individual roles in DNA metabolism, progress toward drugging these motifs and their utility as potential cancer therapeutics. While protein–DNA interactions were initially thought to be undruggable, recent reports of success with molecules targeting OB-fold containing proteins suggest otherwise. The potential for the development of agents targeting OB-folds is in its infancy, but if successful, would expand the opportunities to impinge on genome stability and maintenance pathways for more effective cancer treatment.

show abstract

Diagnostic and prognostic value of MCM3 and its interacting proteins in hepatocellular carcinoma

Cited by 14 publications

References 47 publications

MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation

MCM2-7 in Clear Cell Renal Cell Carcinoma: MCM7 Promotes Tumor Cell Proliferation

A Novel Epigenetic Machine Learning Model to Define Risk of Progression for Hepatocellular Carcinoma Patients

OB-Folds and Genome Maintenance: Targeting Protein–DNA Interactions for Cancer Therapy

Contact Info

Product

Resources

About