Plasma immune analytes in patients with epithelial ovarian cancer.
OBJECTIVE
Inflammation is a common feature of epithelial ovarian cancer (EOC), and measurement of plasma markers of inflammation might identify candidate markers for use in screening or presurgical evaluation of patients with adnexal masses.


METHODS
Plasma specimens from cohorts of 100 patients with advanced EOC (AJCC Stage III and IV), 50 patients with early stage EOC (Stage I and II), and 50 patients with benign surgical conditions were assayed for concentrations of multiple cytokines, toll-like receptor agonists, and vascular growth factors via ELISA and electrochemiluminescence. Immune proteins were then analyzed for association with EOC. Differences in plasma protein levels between benign, early, and advanced EOC patient groups were assessed with and without adjustment for plasma cancer antigen 125 (CA-125) levels.


RESULTS
Out of 23 proteins tested, six-including interferon gamma (IFNγ), interleukin 6 (IL-6), IL-8, IL-10, tumor necrosis factor alpha (TNFα), and placental growth factor (PlGF)-were univariately associated with EOC (all p<0.005), and one-IL-6-was associated with early stage EOC (p<0.0001). Heat shock protein 90kDa beta member 1 (HSP90B1, gp96) was associated with EOC and early stage EOC with borderline statistical significance (p=0.039 and p=0.026, respectively). However, when adjusted for (CA-125), only HSP90B1 independently predicted EOC (p=0.008), as well as early stage EOC (p=0.014).


CONCLUSIONS
Multiple plasma cytokines, including IFNγ, IL-6, IL-8, IL-10, TNFα, PlGF, and HSP90B1 are associated with EOC. Of these, HSP90B1 is associated with EOC independent from the biomarker CA-125.
Department of Oncology, Mayo Clinic, Rochester, MN, United States; Department of Immunology, Mayo Clinic, Rochester, MN, United States. Electronic address: block.matthew@mayo.edu.
Matthew S
MS
Block
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States.
Matthew J
MJ
Maurer
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States.
Krista
K
Goergen
Department of Oncology, Mayo Clinic, Rochester, MN, United States.
Kimberly R
KR
Kalli
Department of Immunology, Mayo Clinic, Rochester, MN, United States.
Courtney L
CL
Erskine
Department of Immunology, Mayo Clinic, Rochester, MN, United States.
Marshall D
MD
Behrens
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, United States.
Ann L
AL
Oberg
Vaccine and Gene Therapy Institute, Port Saint Lucie, FL, United States; Department of Immunology, Mayo Clinic, Rochester, MN, United States.
Keith L
KL
Knutson
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018394:CA-125 Antigen / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D016015:Logistic Models; D008562:Membrane Glycoproteins / Q000097:blood; D008565:Membrane Proteins / Q000097:blood; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000276:immunology*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000276:immunology*
D015415:Biomarkers; D018394:CA-125 Antigen; D016207:Cytokines; C451759:MUC16 protein, human; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C053387:endoplasmin
HSP90B1; Interleukin 6 (IL-6); Ovarian cancer