Abstract
BackgroundmiRNAs and genes can serve as biomarkers for the prognosis and therapy of cervical tumors whose metastasis into lymph nodes is closely associated with disease progression and poor prognosis.MethodsR software and Bioconductor packages were employed to identify differentially expressed miRNAs (DEMs) from The Cancer Genome Atlas (TCGA) database. GEO2R detected differentially expressed genes (DEGs) in the GSE7410 dataset originating from the Gene Expression Omnibus (GEO). A Cox proportional hazard regression model was established to select prognostic miRNA biomarkers. Online tools such as TargetScan and miRDB predicted target genes, and overlapping DEGs and target genes were defined as consensus genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology (GO) function annotations were performed to discern the potential functions of consensus genes. STRING and Cytoscape screened key genes and constructed a regulatory network.ResultsA combination of four miRNAs (down-regulated miR-502 and miR-145, up-regulated miR-142 and miR-33b) was identified as an independent prognostic signature of cervical cancer. A total of 94 consensus genes were significantly enriched in 7 KEGG pathways and 19 GO function annotations including the cAMP signaling pathway, the plasma membrane, integral components of the plasma membrane, cell adhesion, etc. The module analysis suggested that CXCL12, IGF1, PTPRC CDH5, RAD51B, REV3L, and WDHD1 are key genes that significantly correlate with cervical cancer lymph node metastasis.ConclusionsThis study demonstrates that a four-miRNA signature can be a prognostic biomarker, and seven key genes are significantly associated with lymph node metastasis in cervical cancer patients. These miRNAs and key genes have the potential to be therapeutic targets for cervical cancer. Among them, two miRNAs (miR-502 and miR-33b) and two key genes (PTPRC and CDH5) were first reported to be potential novel biomarkers for cervical cancer. The current study further characterizes the progression of lymph node metastasis and mechanism of cervical tumors; therefore, it provides a novel diagnostic indicator and therapeutic targets for future clinical treatments.
Highlights
Worldwide, cervical cancer is the fourth most common female malignancy with an extremely high morbidity and mortality rate (Cohen et al, 2019)
A total of 110 differentially expressed miRNAs (DEMs) were obtained after analyzing miRNA expression profiles from The Cancer Genome Atlas (TCGA) with R language using Padj < 0.05 and |log2FC| > 1 as screening criteria
1840 differentially expressed genes (DEGs) related to early cervical cancer lymph node metastasis were identified by analyzing the GSE7410 expression profile with GEO2R using Padj < 0.05 and |log2FC| > 1 as screening criteria
Summary
Cervical cancer is the fourth most common female malignancy with an extremely high morbidity and mortality rate (Cohen et al, 2019). Yao et al (Yao et al, 2018) demonstrated that decreased expression of HPGD by miR-146b-3p induced proliferation, migration, and anchorage-independent growth of cervical cancer cells by activating the STAT3 and AKT signaling pathways. This indicated that miRNAs may be clinically applicable as potential biomarkers and therapeutic targets. MiRNAs and genes can serve as biomarkers for the prognosis and therapy of cervical tumors whose metastasis into lymph nodes is closely associated with disease progression and poor prognosis
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