title: Inflammation-regulating factors in ascites as predictive biomarkers of drug resistance and progression-free survival in serous epithelial ovarian cancers.
abstract: BACKGROUND
  Platinum-based combination therapy is the standard first-line treatment for women with advanced serous epithelial ovarian carcinoma (EOC). However, about 20 % will not respond and are considered clinically resistant. The availability of biomarkers to predict responses to the initial therapy would provide a practical approach to identify women who would benefit from a more appropriate first-line treatment. Ascites is an attractive inflammatory fluid for biomarker discovery as it is easy and minimally invasive to obtain. The aim of this study was to evaluate whether six selected inflammation-regulating factors in ascites could serve as diagnostic or drug resistance biomarkers in patients with advanced serous EOC.
  
  
  METHODS
  A total of 53 women with stage III/IV serous EOC and 10 women with benign conditions were enrolled in this study. Eleven of the 53 women with serous EOC were considered clinically resistant to treatment with progression-free survival<6 months. Ascites were collected at the time of the debulking surgery and the levels of cytokines were measured by ELISA. The six selected cytokines were evaluated for their ability to discriminate serous EOC from benign controls, and to discriminate platinum resistant from platinum sensitive patients.
  
  
  RESULTS
  Median ascites levels of IL-6, IL-10 and osteoprotegerin (OPG) were significantly higher in women with advanced serous EOC than in controls (P≤0.012). There were no significant difference in the median ascites levels of leptin, soluble urokinase plasminogen activator receptor (suPAR) and CCL18 among serous EOC women and controls. In Receiver Operator curve (ROC) analysis, IL-6, IL-10 and OPG had a high area under the curve value of 0.905, 0.832 and 0.825 respectively for distinguishing EOC from benign controls. ROC analysis of individual cytokines revealed low discriminating potential to stratify patients according to their sensitivity to first-line treatment. The combination of biomarkers with the highest discriminating potential was with CA125 and leptin (AUC=0.936, 95% CI: 0.894-0.978).
  
  
  CONCLUSIONS
  IL-6 was found to be strongly associated with advanced serous EOC and could be used in combination with serum CA125 to discriminate benign and EOC. Furthermore, the combination of serum CA125 and ascites leptin was a strong predictor of clinical resistance to first-line therapy.
authors.affiliation: Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, 3001, 12ième Avenue Nord, J1H 5 N4, Sherbrooke, Canada. dens.lane@usherbrooke.ca.
authors.forename: Denis
authors.initials: D
authors.lastname: Lane
authors.affiliation: Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, 3001, 12ième Avenue Nord, J1H 5 N4, Sherbrooke, Canada. isabelle.matte@usherbrooke.ca.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Matte
authors.affiliation: Département de Pathologie, Faculté de Médecine, Université de Sherbrooke, 3001, 12ième Avenue Nord, J1H 5 N4, Sherbrooke, Canada. perrine.garde-granger@usherbrooke.ca.
authors.forename: Perrine
authors.initials: P
authors.lastname: Garde-Granger
authors.affiliation: Département de Pathologie, Faculté de Médecine, Université de Sherbrooke, 3001, 12ième Avenue Nord, J1H 5 N4, Sherbrooke, Canada. claude.laplante@usherbrooke.ca.
authors.forename: Claude
authors.initials: C
authors.lastname: Laplante
authors.affiliation: Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, 3001, 12ième Avenue Nord, J1H 5 N4, Sherbrooke, Canada. alex.carignan@usherbrooke.ca.
authors.forename: Alex
authors.initials: A
authors.lastname: Carignan
authors.affiliation: Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, 3001, 12ième Avenue Nord, J1H 5 N4, Sherbrooke, Canada. claudine.rancourt@usherbrooke.ca.
authors.forename: Claudine
authors.initials: C
authors.lastname: Rancourt
authors.affiliation: Département de Microbiologie et Infectiologie, Faculté de Médecine, Université de Sherbrooke, 3001, 12ième Avenue Nord, J1H 5 N4, Sherbrooke, Canada. alain.piche@usherbrooke.ca.
authors.forename: Alain
authors.initials: A
authors.lastname: Piché
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000378:metabolism / Q000473:pathology; D001202:Ascitic Fluid / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics*; D018394:CA-125 Antigen / Q000235:genetics*; D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D003937:Diagnosis, Differential; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D015850:Interleukin-6; C451759:MUC16 protein, human; D008565:Membrane Proteins