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Published on: March 14, 2019
Comprehensive miRNA profiling of surgically staged endometrial cancer
David E Cohn1, Muller Fabbri, Nicola Valeri
1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA. David.Cohn@osumc.edu
Objective:
We sought to determine a microRNA (miRNA) profile of surgically staged endometrial cancers.
Study Design:
RNA was extracted from archival primary endometrial cancers, and an miRNA profile was established using a microarray and confirmed with real-time polymerase chain reaction. Targets of differentially expressed miRNAs were explored using real-time polymerase chain reaction and Western blot in endometrial cell lines.
Results:
Endometrial cancer has an miRNA profile distinct from normal endometrium, even in patients with stage IA grade 1 tumors. This miRNA cancer profile was able to correctly assign a specimen as a malignancy with a sensitivity of 92%. Overexpressed miRNAs were predicted to target PTEN, and transfection of cell lines with these miRNAs led to down-regulation of PTEN expression. In advanced disease, an miRNA pattern distinct from early-stage disease was seen, and overexpression of mir-199c predicted improved cancer survival in this population.
Conclusion:
Endometrial cancer has a distinct miRNA profile, and miRNAs can be used as a predictive biomarker.
Insights
Endometrial cancer exhibits a unique microRNA (miRNA) profile, distinguishing it from normal tissue and enabling accurate malignancy identification. Specific miRNA patterns may also predict patient outcomes, highlighting their potential as biomarkers.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Endometrial cancer diagnosis and staging are critical for treatment.
- MicroRNAs (miRNAs) are small non-coding RNAs involved in gene regulation.
- Understanding miRNA expression in endometrial cancer may reveal novel diagnostic and prognostic markers.
Purpose of the Study:
- To define the microRNA (miRNA) profile of surgically staged endometrial cancers.
- To investigate the potential of miRNA profiles as diagnostic biomarkers.
- To explore the relationship between miRNA expression and patient survival.
Main Methods:
- RNA extraction from archival endometrial cancer tissues.
- Microarray analysis to establish miRNA profiles.
- Real-time polymerase chain reaction (PCR) and Western blot for validation and target analysis.
- Transfection studies in endometrial cell lines.
Main Results:
- A distinct miRNA profile was identified in endometrial cancer, differentiating it from normal endometrium with 92% sensitivity.
- Overexpressed miRNAs targeted PTEN, leading to its down-regulation in cell lines.
- Advanced stage disease showed a different miRNA pattern compared to early-stage disease.
- Overexpression of mir-199c was associated with improved survival in advanced endometrial cancer.
Conclusions:
- Endometrial cancer possesses a unique miRNA signature.
- MicroRNAs serve as potential predictive biomarkers for endometrial cancer diagnosis and prognosis.
