| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3942542 | Gynecologic Oncology | 2015 | 10 Pages |
•An 11-gene chemoresistance signature highlights heterogeneity in ovarian carcinoma•APC, MAPK3 and S100A10 are potential biomarkers of poor chemotherapy response in primary serous ovarian carcinoma•Higher BAG3 and APC mRNA and S100A10 protein expression is associated with poor survival in primary serous ovarian carcinoma
ObjectiveTo validate our earlier observation that 11 chemoresistance-associated mRNAs are molecular markers of poor overall survival in ovarian serous carcinoma.MethodsOvarian serous carcinomas (n = 112) and solid metastases (n = 63; total = 175) were analyzed for mRNA expression of APC, BAG3, EGFR, S100A10, ITGAE, MAPK3, TAP1, BNIP3, MMP9, FASLG and GPX3 using quantitative real-time PCR. mRNA expression was studied for association with clinicopathologic parameters and survival. Tumor heterogeneity was assessed in 20 cases with > 1 specimen per patient. APC, BAG3, S100A10 and ERK1 protein expression by immunohistochemistry was analyzed in 58 specimens (38 primary carcinomas, 20 metastases).ResultsBAG3 (p = 0.013), TAP1 (p = 0.014), BNIP3 (p < 0.001) and MMP9 (p = 0.036) were overexpressed in primary tumors, whereas S100A10 (p = 0.027) and FASLG (p = 0.006) were overexpressed in metastases. Analysis of patient-matched primary carcinomas and metastases showed overexpression of APC (p = 0.022), MAPK3 (p = 0.002) and BNIP3 (p = 0.004) in the former. In primary carcinomas, higher APC (p = 0.003) and MAPK3 (p = 0.005) levels were related to less favorable chemoresponse. Higher S100A10 (p = 0.029) and MAPK3 (p = 0.041) levels were related to primary chemoresistance. Higher BAG3 (p = 0.026) and APC (p = 0.046) levels in primary carcinomas were significantly related to poor overall survival in univariate, though not in multivariate survival analysis. S100A10 protein expression was related to poor chemoresponse (p = 0.002) and shorter overall (p = 0.005) and progression-free (p < 0.001) survival, the latter finding retained in multivariate analysis (p = 0.035).ConclusionsOur data provide evidence of heterogeneity in ovarian serous carcinoma and identify APC, MAPK3, BAG3 and S100A10 as potential biomarkers of poor chemotherapy response and/or poor outcome in this cancer.
