Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers.
OBJECTIVE
There are few validated relapse prediction biomarkers for epithelial ovarian cancer (EOC). We have shown progranulin (PGRN) and secretory leukocyte protease inhibitor (SLPI) are up regulated, overexpressed survival factors in EOC. We hypothesized they would predict presence of occult EOC.


METHODS
PGRN, SLPI, and the known biomarker HE4 were measured in EOC patient plasma samples, prospectively collected every 3 months from initial remission until relapse. Clinical data and CA125 results were incorporated into statistical analyses. Exploratory Kaplan-Meier estimates, dividing markers at median values, evaluated association with progression-free survival (PFS) and overall survival (OS). Area-under-the-curve (AUC) statistics were computed from receiver operating characteristic (ROC) curves to evaluate discrimination ability. A Cox proportional hazards model assessed the association between PFS, OS, and biomarkers, adjusting for clinical prognostic factors.


RESULTS
Samples from 23 advanced stage EOC patients were evaluated. PGRN at 3 months was the only biomarker independently associated with PFS (P<0.0001) and OS (P<0.003). When used to predict progression by 18 months, sensitivity and specificity were 93% and 100%, respectively, with AUC=0.944. The Cox model hazard ratio for PFS, divided at 59 ng/ml by ROC analysis and adjusted for clinical factors, was 23.5 (95% CI: 2.49-220). Combinations with SLPI, HE4, and/or CA125 did not improve the model.


CONCLUSIONS
We report pilot data indicating a potential independent association of PGRN on EOC patient PFS and OS. A validation study will be required to confirm this finding and to inform whether PGRN warrants evaluation as a potential screening biomarker.
Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
Jasmine J
JJ
Han
Minshu
M
Yu
Nicole
N
Houston
Seth M
SM
Steinberg
Elise C
EC
Kohn
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D018572:Disease-Free Survival; D030501:Epididymal Secretory Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood; D010051:Ovarian Neoplasms / Q000097:blood*; D011237:Predictive Value of Tests; D000077153:Progranulins; D012372:ROC Curve; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000097:blood; D023083:beta-Defensins
D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C426184:DEFB126 protein, human; D030501:Epididymal Secretory Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D023083:beta-Defensins