Using Weighted Gene Co-Expression Network Analysis to Identify Increased MND1 Expression as a Predictor of Poor Breast Cancer Survival

Abstract

Objective We used bioinformatics analysis to identify potential biomarker genes and their relationship with breast cancer (BC). Materials and Methods We used a weighted gene co-expression network analysis (WGCNA) to create a co-expression network based on the top 25% genes in the GSE24124, GSE33926, and GSE86166 datasets obtained from the Gene Expression Omnibus. We used the DAVID online platform to perform GO and KEGG pathway enrichment analyses and the Cytoscape CytoHubba plug-in to screen the potential genes. Then, we related the genes to prognostic values in BC using the Oncomine, GEPIA, and Kaplan–Meier Plotter databases. Findings were validated by immunohistochemical (IHC) staining in the Human Protein Atlas and the TCGA-BRCA cohort. LinkedOmics identified the interactive expressions of hub genes. We used UALCAN to evaluate the methylation levels of these hub genes. MethSurv and SurvivalMeth were used to assess the multilevel prognostic value. Finally, we assessed hub gene association with immune cell infiltration using TIMER. Results The mRNA levels of MKI67, UBE2C, GTSE1, CCNA2, and MND1 were significantly upregulated in BC, whereas ESR1, THSD4, TFF1, AGR2, and FOXA1 were significantly downregulated. The DNA methylation signature analysis showed a better prognosis in the low-risk group. Further subgroup analyses revealed that MND1 might serve as an independent risk factor for unfavorable BC prognosis. Additionally, MND1 expression levels positively correlate with the immune infiltration statuses of CD4+ T cells, CD8+ T cells, B cells, neutrophils, dendritic cells, and macrophages. Conclusion Our results indicate that the ten hub genes may be involved in BC’s carcinogenesis, development, or metastasis, and MND1 may be a potential biomarker and therapeutic target for BC.

Meiotic nuclear divisions 1 promotes proliferation and metastasis in hepatocellular carcinoma and is a potential diagnostic and therapeutic target gene

“…The results showed that MND1 was highly expressed in many cancers. As previously reported, MND1 was highly expressed in both lung cancer and adenocarcinoma [ 12 , 13 ]. We also found that MND1 is highly expressed in hepatocellular carcinoma and verified the high expression of MND1 in hepatocellular carcinoma cell lines.…”

“…MND1 is a gene that plays a vital role in meiosis [ 27 – 30 ], but its relationship with cancer is unclear. Although it has been reported to be associated with lung cancer, breast cancer, and renal clear cell carcinoma [ 12 , 13 , 31 ], the relationship between MND1 and cancer has not been well explained [ 32 ]. Ultimately, we selected one MND1 as our study subject.…”

“…We found that these genes are correlated, which further proves our conclusion. One study reported an association between the high expression of MND1 and the immune microenvironment in breast cancer [ 13 ]. Similar to previous results, we also obtained consistent results in hepatocellular carcinoma.…”

“…Meiotic nuclear divisions 1 (MND1) is a protein coding gene considered crucial for meiotic homology repair [ 11 ]. Several recent studies have demonstrated that MND1 messenger RNA (mRNA) levels are elevated in lung cancer and breast cancer, which means MND1 mRNA level is considered a prognostic factor for lung cancer and breast cancer [ 12 , 13 ]. In addition, MND1 has also been proven to promote the cell cycle in lung cancer by activating the KLF6/E2F1-positive feedback loop [ 14 ].…”

High Expression of DNTTIP1 Predicts Poor Prognosis in Clear Cell Renal Cell Carcinoma

“…45 MKI67 and MMPs could promote the progress of tumor, were the potential biomarker for clinical examination of malignant characteristics in tumors. [46][47][48] Here, we show that DNTTIP1 was associated with EMT in Ss-GSEA and GSEA. DNTTIP1 expression had a positive correlation with oncogene of snail1, twist1, vim, MKI67, and MMP2, but had a negative correlation with E-cadherin (E-cad).…”