Identification of potential biomarkers in cervical cancer with combined public mRNA and miRNA expression microarray data analysis

Abstract

Cervical cancer is the fourth most prevalent malignancy in females worldwide. Early diagnosis is key to improving survival rates. Molecular biomarkers are an important method for diagnosing a number of types of cancer, including cervical cancer. The present study utilized public data from three mRNA microarray datasets and one microRNA dataset to analyze the key genes involved in cervical cancer. The mRNA and microRNA expression profile datasets (GSE9750, GSE46857, GSE67522 and GSE30656) were downloaded from the Gene Expression Omnibus database (GEO). Differentially expressed genes (DEGs) and microRNAs (DEMs) were screened using the online tool GEO2R. By using the DEGs consistent across the three mRNA datasets, a functional and pathway enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed and module analysis performed using the Search Tool for the Retrieval of Interacting Genes. Validated target genes of the DEMs were identified using the miRecords website. Using the identified target genes of the DEMs, a survival analysis was performed using the OncoLnc online tool. A total of 73 DEGs and 19 DEMs were screened from the microarray expression profile datasets. ‘Integrin-mediated’, ‘proteolysis’ and ‘phosphoinositide 3 kinase-protein kinase 3’ signaling pathways were the most enriched in the DEGs. Three of the DEGs, including Ras homolog family member B (RhoB), stathmin 1 (STMN1) and cyclin D1 (CCNB1) were validated DEM target genes. The OncoLnc survival analysis identified that RhoB was associated with a significantly longer overall survival, whereas STMN1 was associated with a significantly reduced overall survival time in patients with cervical cancer. Finally, data from The Cancer Genome Atlas revealed an association between the mRNA expression levels of RhoB and STMN1, and the overall survival time for patients with cervical cancer. In conclusion, RhoB and STMN1 were identified as key genes that may provide potential targets for cervical cancer diagnosis and treatment.

Increased miR-20b Level in High Grade Cervical Intraepithelial Neoplasia

“…miRNAs may act as "oncomirs" functioning as either oncogenes or tumor suppressors depending on the type of tissue and stage of tumor development. miRNAs may be upor downregulated in cancer tissue and thus these molecules have been suggested to be potential novel tumor markers [3,13,14,17,19,[24][25][26][27][28]. Accordig to Pardini et al, 24 studies targeting miRNA expression in cervical cancer show "great variability".…”

“…[6,[8][9][10] Several new biomarkers have been applied for detection of transformed cells aiming to increase the sensitivity and/or specificity of the screening tests and/or in combination with cytology and/or with HPV DNA testing [8,11]. More recently, several groups have demonstrated aberrant expression of microRNAs (miRNAs) in premalignant and malignant cervical lesions, suggesting that this might be used as a more specific biomarker [3,[12][13][14][15][16][17][18][19]. The majority of these works analyzed cervical cancer and/or premalignant lesions, with no surrounding tumor-free tissues coming from the same patient.…”

<p>Identification of candidate biomarkers correlated with the diagnosis and prognosis of cervical cancer via integrated bioinformatics analysis</p>

“…OncoLnc database (www.oncolnc.org) contains survival data for 8,647 patients from 21 cancer studies from TCGA 6. The tool was used to conduct an overall survival analysis (OS) for patients with cervical cancer.…”

“…At present, a large number of studies on the expression profile of cervical cancer have been carried out to identify the differentially expressed genes (DEGs) related to the development process or prognosis of cancer. However, owing to different data processing methods and different sample sizes, the results of DEGs are incompatible and even contradictory 6,7. Therefore, the results obtained by different raw data processing methods still have some limitations and insufficiency.…”

Recent Advances on the Molecular Mechanism of Cervical Carcinogenesis Based on Systems Biology Technologies

“…RhoB (Ras homolog family member B), stathmin 1 and cyclin D1 were found to be key genes in cervical cancer progression. Moreover, RhoB and stathmin 1 were identified as potential biomarkers for diagnosis and treatment of cervical cancer [70]. The microarray analysis was also used for the prediction of lymph node metastasis in cervical cancer patients.…”