Increased EZH2 protein expression correlates with a better disease-free survival in ovarian cancer patients

75% of ovarian cancer patients will develop recurrent disease with a median survival of 12 – 24 months. There is still no biomarker to predict efficacy of ovarian cancer (OC) treatment. The protein array method DigiWest detected EZH2 to be highly expressed in therapy sensitive OC. We compared if EZH2 levels determined by DigiWest are superior to classical protein assessment of histological tumor samples using Immunoreactive Score (IRS) to predict disease free survival (DFS) of OC patients.

DigiWest was used to analyze 500 proteins in 17 fresh frozen tumor samples obtained from OC patients with DFS periods ranging from 4 to 78 months post-surgery. Further 125 FFPE samples from tumor patients with DFS periods ranging from 2 to 55 months were stained by immunohistochemistry (IHC) for EZH2 and scored. An independent RNA expression data set (TCGA, n = 616) was used to correlate EZH2 mRNA expression to patients' DFS via survival analysis (Log-Rank).

Kaplan-Meier survival analysis displayed a significantly better DFS of OC patients with high EZH2 protein expression (p = 0.0067) determined by DigiWest. In contrast, IRS of EZH2 in FFPE tissues did not correlate with increased DFS. EZH2 mRNA expression was associated with higher DFS periods (p = 0.023).

Analysis of EZH2 protein levels by DigiWest and of EZH2 mRNA, but not protein analysis by IHC, correlate with DFS of OC patients. This suggests that protein analysis with DigiWest may have high diagnostic power. EZH2 measured by DigiWest could be used as a potential biomarker for determination of therapy efficacy.