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Expression and clinical role of chemoresponse-associated genes in ovarian serous carcinoma
- Source :
- Gynecologic Oncology. 139:30-39
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- Objective To validate our earlier observation that 11 chemoresistance-associated mRNAs are molecular markers of poor overall survival in ovarian serous carcinoma. Methods Ovarian 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). Results BAG3 (p=0.013), TAP1 (p=0.014), BNIP3 (p 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 Conclusions Our 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.
- Subjects :
- Adult
Oncology
medicine.medical_specialty
MAPK3
Adenomatous Polyposis Coli Protein
Gene Expression
MMP9
ITGAE
Internal medicine
Biomarkers, Tumor
medicine
Humans
RNA, Messenger
Annexin A2
Adaptor Proteins, Signal Transducing
Aged
Aged, 80 and over
Ovarian Neoplasms
Mitogen-Activated Protein Kinase 3
business.industry
S100 Proteins
Obstetrics and Gynecology
Cancer
Middle Aged
Prognosis
medicine.disease
Cystadenocarcinoma, Serous
Serous fluid
Real-time polymerase chain reaction
Drug Resistance, Neoplasm
Immunohistochemistry
Female
TAP1
Apoptosis Regulatory Proteins
business
Subjects
Details
- ISSN :
- 00908258
- Volume :
- 139
- Database :
- OpenAIRE
- Journal :
- Gynecologic Oncology
- Accession number :
- edsair.doi.dedup.....187c00dc3f3dd331c9e64cd73b2d91ec