title: Clinical relevance of multidrug resistance gene expression in ovarian serous carcinoma effusions.
abstract: The presence of tumor cells in effusions within serosal cavities is a clinical manifestation of advanced-stage cancer and is generally associated with poor survival. Identifying molecular targets may help to design efficient treatments to eradicate these aggressive cancer cells and improve patient survival. Using a state-of-the-art TaqMan-based qRT-PCR assay, we investigated the multidrug resistance (MDR) transcriptome of 32 unpaired ovarian serous carcinoma effusion samples obtained at diagnosis or at disease recurrence following chemotherapy. MDR genes were selected a priori based on an extensive curation of the literature published during the last three decades. We found three gene signatures with a statistically significant correlation with overall survival (OS), response to treatment [complete response (CR) vs other], and progression free survival (PFS). The median log-rank p-values for the signatures were 0.023, 0.034, and 0.008, respectively. No correlation was found with residual tumor status after cytoreductive surgery, treatment (with or without chemotherapy) and stage defined according to the International Federation of Gynecology and Obstetrics. Further analyses demonstrated that gene expression alone can effectively predict the survival outcome of women with ovarian serous carcinoma (OS, log-rank p = 0.0000; and PFS, log-rank p = 0.002). Interestingly, the signature for overall survival is the same in patients at first presentation and those who had chemotherapy and relapsed. This pilot study highlights two new gene signatures that may help in optimizing the treatment for ovarian carcinoma patients with effusions.
authors.affiliation: Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gillet
authors.forename: Junbai
authors.initials: J
authors.lastname: Wang
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Calcagno
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Green
authors.forename: Sudhir
authors.initials: S
authors.lastname: Varma
authors.forename: Mari
authors.initials: M
authors.lastname: Bunkholt Elstrand
authors.forename: Claes G
authors.initials: CG
authors.lastname: Trope
authors.forename: Suresh V
authors.initials: SV
authors.lastname: Ambudkar
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
authors.forename: Michael M
authors.initials: MM
authors.lastname: Gottesman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018284:Cystadenocarcinoma, Serous / Q000235:genetics*; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics*; D010865:Pilot Projects; D016133:Polymerase Chain Reaction