title: Cytokine profiling of ascites at primary surgery identifies an interaction of tumor necrosis factor-α and interleukin-6 in predicting reduced progression-free survival in epithelial ovarian cancer.
abstract: OBJECTIVE
  Epithelial ovarian cancer (EOC) typically presents with advanced disease. Even with optimal debulking and response to adjuvant chemotherapy, the majority of patients will have disease relapse. We evaluated cytokine and chemokine profiles in ascites at primary surgery as biomarkers for progression-free survival (PFS) and overall survival (OS) in patients with advanced EOC.
  
  
  METHODS
  Retrospective analysis of patients (n =70) who underwent surgery at Roswell Park Cancer Institute between 2002 and 2012, followed by platinum-based chemotherapy.
  
  
  RESULTS
  The mean age at diagnosis was 61.8 years, 85.3% had serous EOC, and 95.7% had stage IIIB, IIIC, or IV disease. Univariate analysis showed that ascites levels of tumor necrosis factor (TNF)-α were associated with reduced PFS after primary surgery. Although the ascites concentration of interleukin (IL)-6 was not by itself predictive of PFS, we found that stratifying patients by high TNF-α and high IL-6 levels identified a sub-group of patients at high risk for rapid disease relapse. This effect was largely independent of clinical prognostic variables.
  
  
  CONCLUSIONS
  The combination of high TNF-α and high IL-6 ascites levels at primary surgery predicts worse PFS in patients with advanced EOC. These results suggest an interaction between ascites TNF-α and IL-6 in driving tumor progression and resistance to chemotherapy in advanced EOC, and raise the potential for pre-treatment ascites levels of these cytokines as prognostic biomarkers. This study involved a small sample of patients and was an exploratory analysis; therefore, findings require validation in a larger independent cohort.
authors.affiliation: Department of Gynecology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Nonna
authors.initials: N
authors.lastname: Kolomeyevskaya
authors.affiliation: Department of Biostatistics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kevin H
authors.initials: KH
authors.lastname: Eng
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Anm Nazmul H
authors.initials: AN
authors.lastname: Khan
authors.affiliation: Department of Gynecology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kassondra S
authors.initials: KS
authors.lastname: Grzankowski
authors.affiliation: Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Singel
authors.affiliation: Department of Epidemiology and Population Sciences, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Moysich
authors.affiliation: Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA; Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY, USA; Department of Medicine,University at Buffalo School of Medicine, Buffalo, NY, USA. Electronic address: brahm.segal@roswellpark.org.
authors.forename: Brahm H
authors.initials: BH
authors.lastname: Segal
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000276:immunology / Q000378:metabolism; D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D010051:Ovarian Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha
keywords: Ascites; IL-6; Ovarian cancer; Prognosis; TNF-α