Abstract
With the goal of identifying diagnostic and prognostic biomarkers in endometrial cancer, miRNA-profiling was carried out with formalin-fixed paraffin embedded (FFPE) tissue samples from 49 endometrial cancer patients. Results using an 84-cancer specific miRNA panel identified the upregulation of miR-141-3p and miR-96-5p along with a downregulation of miR-26, miR-126-3p, miR-23b, miR-195-5p, miR-374a and let-7 family of miRNAs in endometrial cancer. We validated the dysregulated expression of the identified miRNAs in a panel of endometrial cancer cell-lines. Immunohistochemical analysis of the tissue micro array derived from these patients established the functional correlation between the decreased expression of tumor suppressive miRNAs and their target oncogenes: ERBB2, EGFR, EPHA2, BAX, GNA12, GNA13, and JUN. Comparative analysis of the samples from the patients with extended progression-free survival (PFS) ( > 21 months) versus the patients with the PFS of < 21 months indicated increased expression of tumor suppressive miR-142-3p, miR-142-5p, and miR-15a-5p in samples from extended PFS patients. In addition to defining a specific set of miRNAs and their target genes as potential diagnostic biomarkers, our studies have identified tumor suppressive miR-142 cluster and miR-15a as predictors of favorable prognosis for therapy response in endometrial cancer.
Highlights
Endometrial cancer is one of the major gynecological cancer that will be affecting more than 61,000 patients with the anticipated death of 10,920 patients in 2017 [1]
With the goal of identifying such a prognostic marker, we focused on defining the changes in miRNA profiles that could be associated with therapy resistance in endometrial cancer patients
We investigated the changes in miRNA profiles using formalin-fixed paraffin embedded (FFPE)-samples derived from a cohort of endometrial cancer patients
Summary
Endometrial cancer is one of the major gynecological cancer that will be affecting more than 61,000 patients with the anticipated death of 10,920 patients in 2017 [1]. Using FFPE-samples from patients who had progressive disease during or shortly following www.impactjournals.com/Genes&Cancer chemotherapy and patients who remained without disease recurrence, expression profiles of miRNAs were analyzed using a cancer-specific 84-miRNA analysis panel. Our results presented here indicates that the endometrial cancer tissues showed an increase in the expression of several oncomiRs with a concomitant decrease in the expression of tumor suppressor miRNAs compared to control samples.
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