title: MicroRNA let-7a: a potential marker for selection of paclitaxel in ovarian cancer management.
abstract: OBJECTIVE
  Let-7 is a family of small non-coding RNAs regulating the expression of many genes that control important cellular activities. Let-7 is shown in vitro to sensitize cancer cells to platinum, but induce ovarian cancer resistance to paclitaxel. This study aims to investigate the effect of let-7a expression on survival outcomes of epithelial ovarian cancer (EOC) patients treated with different chemotherapy.
  
  
  METHODS
  Let-7a expression was measured with qRT-PCR in ovarian tumors of 178 EOC patients who received platinum-based chemotherapy with and without paclitaxel after surgery. Survival analysis was performed to assess the effects of let-7a and chemotherapy on disease outcomes.
  
  
  RESULTS
  Let-7a expression was detectable in the EOC samples, but the expression was not associated with disease stage, tumor grade, histology and debulking results. Patients who responded to platinum with paclitaxel had significantly lower let-7a than those who did not. Survival analyses showed that patients with high let-7a had better survival compared to those with low let-7a when they were treated with platinum without paclitaxel. The hazards ratios (HRs) for death and disease progression were 0.52 (95% CI: 0.29-0.96) and 0.48 (0.26-0.89) for high let-7a when compared to low let-7a, respectively. However, when patients were treated with platinum and paclitaxel, high let-7a was associated with worse progression-free and overall survival. The HRs for death and disease progression were 3.87 (95% CI: 1.28-11.66) and 3.48 (95% CI: 1.25-9.67) for high let-7a when compared to low let-7a, respectively. Further studies showed that among patients with low let-7a, those treated with paclitaxel in addition to platinum survived better than those treated without paclitaxel [adjusted-HRs were 0.31 (95% CI: 0.15-0.66) for death and 0.40 (95% CI: 0.22-0.75) for disease], while among those with high let-7a, the two types of treatment made no difference in patient survival.
  
  
  CONCLUSIONS
  The study suggests that the beneficial impact of the addition of paclitaxel on EOC survival was significantly linked to let-7a levels, and that miRNAs such as let-7a may be a useful marker for selection of chemotherapeutic agents in EOC management.
authors.affiliation: Department of Epidemiology and Public Health, Yale Cancer Center, Yale University School of Medicine, New Haven, CT 06520-8034, USA.
authors.forename: Lingeng
authors.initials: L
authors.lastname: Lu
authors.forename: Peter
authors.initials: P
authors.lastname: Schwartz
authors.forename: Luca
authors.initials: L
authors.lastname: Scarampi
authors.forename: Thomas
authors.initials: T
authors.lastname: Rutherford
authors.forename: Emilie Marion
authors.initials: EM
authors.lastname: Canuto
authors.forename: Herbert
authors.initials: H
authors.lastname: Yu
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017239:Paclitaxel / Q000627:therapeutic use*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human; D017239:Paclitaxel