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pmid:31354287
Identification of candidate biomarkers correlated with the diagnosis and prognosis of cervical cancer via integrated bioinformatics analysis.
Fangfang Dai · Gantao Chen · Yanqing Wang · Li Zhang · Youmei Long · Mengqin Yuan · Dongyong Yang · Shiyi Liu · Yanxiang Cheng · Liping Zhang
OncoTargets and therapy · 2019 doi:10.2147/OTT.S199615
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Complete file
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Early diagnosis and early treatment can reduce the mortality rate of cervical cancer. However, there is still no specific biomarkers for the diagnosis and detection of cervical cancer prognosis. Therefore, it is greatly urgent in searching biomarkers correlated with the diagnosis and prognosis of cervical cancer. Results: The mRNA and microRNA expression profile datasets (GSE7803, GSE9750, GSE63514, and GSE30656) were downloaded from the Gene Expression Omnibus database (GEO). The three microarray datasets were integrated to one via integrated bioinformatics. Differentially expressed genes (DEGs) and microRNAs (DEMs) were obtained by R software. The protein-protein interaction (PPI) networks of the DEGs were performed from the STRING database and further visualized by Cytoscape software. A total of 83 DEGs and 14 DEMs were screened from the microarray expression profile datasets. The miRNAs validated to be associated with cervical cancer were obtained using HMDD online website and the target genes of DEMs were identified using the miRWalk2.0 online database. ESR1, PPP1R3C, NSG1, and TMPRSS11D were the gene targets of hsa-miR-21; the targets of hsa-miR-16 were GYS2, ENDOU, and KLF4. These targets were all downregulated in cervical cancer. Finally, we verified the expression of those targets in cervical tissues from TCGA and GTEx databases and analyzed their relationship with survival of cervical cancer patients. In the end, the expression of key genes in cervical cancer tissues was verified via experiment method, we found KLF4 and ESR1 were downregulated in tumor tissues. Conclusion: This study indicates that KLF4 and ESR1 are downregulated by the upregulated miR21 and miRNA16 in cervical cancer, respectively, using bioinformatics analysis, and the lower expression of KLF4 and ESR1 is closely related to the poor prognosis. They might be of clinical significance for the diagnosis and prognosis of cervical cancer, and provide effective targets for the treatment of cervical cancer.", "claims": [{"id": "claim-method", "statement": "GraphPad Prism5 was used for statistical analysis, independent samples t-test was used to analyze the correlation between KLF4, ESR1 expression, and tissue parameters.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31354287", "locator": "sections[10] \"Statistical analysis\" paragraph 2", "quote": "GraphPad Prism5 was used for statistical analysis, independent samples t-test was used to analyze the correlation between KLF4, ESR1 expression, and tissue parameters."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The platform for GSE7803 is GPL96, [HG-U133A] Affymetrix Human Genome U133A Array, which contains 10 normal cervical samples and 21 cervical cancer specimens;", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31354287", "locator": "sections[3] \"Microarray data\" paragraph 2", "quote": "The platform for GSE7803 is GPL96, [HG-U133A] Affymetrix Human Genome U133A Array, which contains 10 normal cervical samples and 21 cervical cancer specimens;"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31354287"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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{"label": "Table 4", "caption": "miRNAs which have been reported and validated in cervical cancer", "rows": [["MiRNAs which have been reported and validated in cervical cancer"], ["hsa-let-7a", "hsa-miR-107", "hsa-miR-10b", "hsa-miR-124", "hsa-miR-125b", "hsa-miR-130a", "hsa-miR-138"], ["hsa-miR-143", "hsa-miR-145", "hsa-miR-146a", "hsa-miR-146b", "hsa-miR-150", "hsa-miR-152", "hsa-miR-155"], ["hsa-miR-15b", "hsa-miR-16", "hsa-miR-195", "hsa-miR-19a", "hsa-miR-200a", "hsa-miR-200b", "hsa-miR-204"], ["hsa-miR-205", "hsa-miR-21", "hsa-miR-210", "hsa-miR-214", "hsa-miR-215", "hsa-miR-218", "hsa-miR-218"], ["hsa-miR-218–2", "hsa-miR-27b", "hsa-miR-29a", "hsa-miR-29c", "hsa-miR-31", "hsa-miR-320", "hsa-miR-328"], ["hsa-miR-34a", "hsa-miR-373", "hsa-miR-376c", "hsa-miR-425", "hsa-miR-429", "hsa-miR-483", "hsa-miR-634"], ["hsa-miR-644a", "hsa-miR-744", "hsa-miR-9", "hsa-miR-93", "hsa-miR-98", "", ""]], "row_count": 8, "column_count": 7, "numeric_cells": 47, "header_rows": 1, "locator": 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