MicroRNA profile of paclitaxel-resistant serous ovarian carcinoma based on formalin-fixed paraffin-embedded samples

Abstract

BackgroundTo assess the feasibility of validating microRNA (miRNA) profile related to paclitaxel-sensitivity in formalin-fixed paraffin-embedded (FFPE) samples of serous ovarian carcinoma (OC) patients.MethodsDeregulated miRNAs identified by miRNA microarray were further detected in 45 FFPE OC samples using Realtime PCR. Correlations between paired FFPE and frozen tumor samples were analyzed. Survival times were compared between 6 high and low miRNAs groups. Western blot and luciferase reporter assay were used for validating the target of miRNA.ResultsSixteen up-regulated miRNAs and twenty-three down-regulated miRNAs were revealed in pacilitaxel-resistant ST30 cells. The up-regulated miRNAs (miR-320a, 22 and 129-5p) and down-regulated miRNAs (miR-9, 155 and 640) were confirmed in paclitaxel-resistant FFPE tumor samples, compared with paclitaxel-sensitive samples. Higher miR-9 and miR-640 showed better survival time in OC patients. Expressions of miR-9, 155 and 22 in FFPE samples were closely mimicked by those in frozen tissues. RAB34 was validated as a direct target of miR-9.ConclusionsWe validated miRNA profile in pacilitaxel-resistant OC using FFPE samples, which might enable treatment stratification and help us to predict outcomes in OC patients. FFPE samples are feasible materials for miRNA research.

Expression of miR-146a in patients with ovarian cancer and its clinical significance

“…A number of other miRs were studied, and the levels of these miRs were correlated with the hazard ratio for patient survival or tumor recurrence (22). In vitro and in vivo studies have suggested that the pattern of miR expression may have an impact on the chemosensitivity of ovarian tumors (23)(24)(25)(26). Vang et al (27) performed a study on a small group of patients with advanced ovarian serous cancer: The study revealed dysregulation of miR-146a and miR-150 in omental metastases and suggested their possible role in increased platinum tolerance (27).…”

MicroRNAs expression profile of gefitinib resistant non-small cell lung cancer HCC827 cells

“…Varying levels of sensitivity to chemotherapy and radiotherapy may be interred by the influence of up-regulation and down-regulation on miRNA on multiple mRNA targets and subsequent protein expression suggesting that the cellular response to chemotherapy and radiotherapy by the dysregulation of survival pathways, cell death, resistance, DNA repair system and/or metabolism [12,5,18,14,15,20]. The profile of miRNAs expression significantly associated with resistance of chemotherapy and radiotherapy was investigated in various kinds of cancer as ovarian cancer, bladder carcinoma and NSCLC [18,14,15,20].…”

“…Varying levels of sensitivity to chemotherapy and radiotherapy may be interred by the influence of up-regulation and down-regulation on miRNA on multiple mRNA targets and subsequent protein expression suggesting that the cellular response to chemotherapy and radiotherapy by the dysregulation of survival pathways, cell death, resistance, DNA repair system and/or metabolism [12,5,18,14,15,20]. The profile of miRNAs expression significantly associated with resistance of chemotherapy and radiotherapy was investigated in various kinds of cancer as ovarian cancer, bladder carcinoma and NSCLC [18,14,15,20]. For example; Sorrentino et al (2008) [18] reported that five miRNAs (miRNA-let-7e, miR-30c, miR-125b, miR-130a and miR-335) were always diversely expressed in all the resistant ovarian cancer A2780 cell lines (A2780TAX, A2780TC1 and T2780CT3 (paclitaxel-resistant A2780) and A2780CIS (cisplatin-resistant A2780); miRNAlet-7e was up-regulated in A2780TAX cell line, while it was down-regulated in A2780TC1, A2780TC3 and A2780CIS cell lines; miR-125b was down-regulated in A2780TAX cell line but up-regulated in A2780TC1, A2780TC3 and A2780CIS cell lines; miR-30c, miR-130a and miR-335 were down-regulated in all resistant ovarian cancer A2780 cell lines suggesting that a direct involvement of miRNAs in the development of chemoresistance.…”

“…Moreover, the profiles of miRNA expression are very helpful for investigation of the prognosis and chemosensitivity as well as radiotherapy of human cancer. There are few studies showing miRNA expression patterns associated with chemotherapy and radiotherapy resistance in various kinds of cancer as the profile of miRNA expression in chemotherapy drugs (Cisplatin, Paclitaxel, and/or Cyclosporin A)-resistant ovarian cancer A2780 cell line [18]; the miRNA expression profile to predict gemcitabine resistance in Bladder carcinoma cell lines as RT4, J82 and TCCSUP cell lines [14]; the miRNA profile of paclitaxel-resistant serous ovarian carcinoma based on formalin-fixed paraffin embedded samples [15]; and miRNA expression and function in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer [20]. Then, investigation of the miRNA expression profile in gefitinib resistance in NSCLC by using miRNA microarray will be useful to overcome the resistance of gefitinib in NSCLC.…”

Prognostic Value of microRNA-224 in Various Cancers: A Meta-analysis

“…Finally, the remaining 20 publications [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] were combined in the meta analysis and the selection process presented by a flow chart which is shown in Fig. 1.…”