Bioinformatics analysis of the transcriptional expression of minichromosome maintenance proteins as potential indicators of survival in patients with cervical cancer

Abstract

Background As major regulators of DNA replication in eukaryotes, minichromosome maintenance (MCM) proteins play an important role in the initiation and extension of DNA replication. MCMs and their related genes may be new markers of cell proliferation activity, which is of great significance for the diagnosis and prognosis of cervical cancer. Methods To explore the role of MCMs and their related genes in cervical cancer, various bioinformatics methods were performed. First, the ONCOMINE and UALCAN databases were used to analyze the mRNA expression of different MCMs. The Human Protein Atlas database was used to analyze the protein expression of MCMs in normal and tumor tissues. The potential clinical value of MCMs was evaluated using the UALCAN, Kaplan-Meier plotter and cBioPortal databases. Then, the related genes and key coexpressed genes of MCMs were screened using GEPIA2 and cBioPortal analysis. For these genes, we used Metascape and the DAVID database to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, construct the related molecular interaction network, and obtain the key subnetworks and related hub genes. The Kaplan-Meier plotter database was used for survival analysis of cervical cancer patients to evaluate and predict the potential clinical value of the hub genes. Moreover, multiple gene comparisons of the expression of MCMs and related genes in different cancer types also showed the clinical significance of these potential targets. Results The mRNA and protein expression of MCMs increased in tumor tissue. Overexpression of MCM2/3/4/5/6/7/8/10 was found to be significantly associated with clinical cancer stage. Higher mRNA expression levels of MCM3/5/6/7/8 were found to be significantly associated with longer overall survival, and higher mRNA expression of MCM2/3/4/5/6/7/8 was associated with favorable OS. In addition, a high mutation rate of MCMs (71%) was observed. MCM2, MCM4, MCM8, MCM3 and MCM7 were the five genes with the most genetic alterations. In addition, the coexpressed genes and related genes of MCMs were successfully screened for enrichment analysis. These genes were significantly enriched in important pathways, such as the DNA replication, cell cycle, mismatch repair, spliceosome, and Fanconi anemia pathways. A protein-protein interaction network was successfully constructed, and a total of 13 hub genes (CDC45, ORC1, RPA1, CDT1, TARDBP, RBMX, SRSF3, SRSF1, RFC5, RFC2, MSH6, DTL, and MSH2) from 4 key subnetworks were obtained. These genes and MCM2/3/4/5/6/7/8 might have potential clinical value for the survival and prognosis of cervical cancer patients. Conclusions These findings promoted the understanding of the MCM protein family and clinically related molecular targets for cervical epithelial neoplasia and cervical cancer. Our results were helpful to evaluate the potential clinical value of MCMs and related genes in patients with cervical cancer.

Bioinformatics Screening of Potential Biomarkers from mRNA Expression Profiles to Discover Drug Targets and Agents for Cervical Cancer

“…On the other hand, we reviewed 52 published articles associated with CC infections that provided transcriptome-guided hub proteins (genomic biomarkers) for cross-validation of the proposed key genes and the candidate drug agents. There were 255 hub genes reported in those 52 articles, with 7 hub proteins (AURKA, PCNA, CCNB1, CDC45, MCM2, TOP2A, CDK1) appearing in at least 5 articles ( Table S2 ) [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 23 , 24 , 25 , 26 , 27 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ]. Five (AURKA, CCNB1, MCM2, TOP2A, and CDK1) of the seven reported hub proteins were found to be similar to our suggested seven KGs.…”

Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma

“…Several studies have reported that abnormal expression of MCM4 is associated with poor prognosis in patients with a variety of tumors (Liu et al, 2021;Wu and Xi, 2021). Xu et al (2021) found that patients with MCM4 high expression hepatocellular carcinoma had more advanced clinical stage and shorter survival time, and silencing MCM4 significantly inhibited the proliferation of hepatocellular carcinoma cells and the growth of hepatocellular carcinoma transplantation tumors.…”

Bioinformatic Investigation of Micro RNA-802 Target Genes, Protein Networks, and Its Potential Prognostic Value in Breast Cancer

“…In lung cancer, SNRPE and MED13L had been reported as potential prognostic markers 70 , 71 . Furthermore, it has been indicated that CASC3, AGO3 and TARDBP could have a significant role in the prognosis of gastric cancer, hepatocellular carcinoma and cervical cancer respectively 72 – 74 .…”