Plasma concentrations of the vitamin E-binding protein afamin are associated with overall and progression-free survival and platinum sensitivity in serous ovarian cancer--a study by the OVCAD consortium.
OBJECTIVE
Comparative proteomics identified the plasma protein afamin as potential biomarker for ovarian cancer (OC). Significantly decreased afamin plasma concentrations in pre-therapeutic OC patients reconstituted to control values after successful tumor surgery. This study evaluates the association of afamin with survival and response to therapy in serous OC patients within the OVCAD consortium project.


METHODS
We measured afamin in 215 pre-therapeutic plasma samples, 246 tumor lysates and 109 plasma samples taken 6months after finishing platinum-based chemotherapy. Differences in afamin plasma concentrations among FIGO stages were tested by Kruskal-Wallis test; association of afamin concentrations with overall and progression-free survival was evaluated using Kaplan-Meier survival plots and multivariate adjusted COX regression analysis.


RESULTS
Pre-therapeutic afamin correlated significantly with FIGO stages (p=0.012) and was lower in the presence of metastases (p=0.013) and poorly differentiated OC in patients responding to therapy (p=0.016). Afamin ≥48.0mg/L was also associated with a lower hazard ratio for recurrent disease as compared to afamin <48.0mg/L (p=0.007). Post-therapeutic afamin ≥48mg/L was positively correlated with overall (p<0.001) and progression-free (p=0.012) survival and was lower in non-responders than in responders (p=0.048). Thus, afamin returned post-therapeutically to values of healthy controls in responders (p<0.001) but not in non-responders (p=0.114). Afamin in tumor lysates was lower in poorly differentiated OC than in G 1+2 tumors (p=0.041). Higher afamin concentrations in tumor lysates were associated with increased overall survival (p=0.003).


CONCLUSIONS
These data indicate that afamin is associated with therapy response and survival rate in advanced OC patients.
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Austria; Department of Internal Medicine, Innsbruck Medical University, Austria.
Andreas
A
Melmer
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Austria.
Linda
L
Fineder
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Austria.
Claudia
C
Lamina
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Austria.
Barbara
B
Kollerits
Department of Laboratory Medicine, Konventhospital Barmherzige Brüder, Linz, Austria.
Benjamin
B
Dieplinger
Department of Gynecology, Campus Virchow-Klinikum, Charité University Hospital, European Competence Center for Ovarian Cancer Berlin, Germany.
Ioana
I
Braicu
Department of Gynecology, Campus Virchow-Klinikum, Charité University Hospital, European Competence Center for Ovarian Cancer Berlin, Germany.
Jalid
J
Sehouli
Division of Gynecological Oncology, Department of Obstetrics and Gynecology and Leuven Cancer Institute, Leuven University Hospitals, Katholieke Universiteit of Leuven, Belgium.
Isabelle
I
Cadron
Division of Gynecological Oncology, Department of Obstetrics and Gynecology and Leuven Cancer Institute, Leuven University Hospitals, Katholieke Universiteit of Leuven, Belgium.
Ignace
I
Vergote
Department of Gynecology, Hamburg-Eppendorf University Medical Center, University Cancer Center Hamburg-Eppendorf (UCCH), Germany.
Sven
S
Mahner
Department of Gynecology and Obstetrics, Innsbruck Medical University, Austria.
Alain G
AG
Zeimet
Department of Obstetrics and Gynecology, Molecular Oncology Group, Vienna Medical University, Austria.
Dan Cacsire
DC
Castillo-Tong
Department of Internal Medicine, Innsbruck Medical University, Austria.
Christoph F
CF
Ebenbichler
Department of Obstetrics and Gynecology, Molecular Oncology Group, Vienna Medical University, Austria.
Robert
R
Zeillinger
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Austria; Vitateq Biotechnology GmbH, Innsbruck, Austria. Electronic address: hans.dieplinger@i-med.ac.at.
Hans
H
Dieplinger
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D018394:CA-125 Antigen / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D018284:Cystadenocarcinoma, Serous / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D012709:Serum Albumin; D000075462:Serum Albumin, Human
C088246:AFM protein, human; D018394:CA-125 Antigen; D002352:Carrier Proteins; D006023:Glycoproteins; D009944:Organoplatinum Compounds; D012709:Serum Albumin; D000075462:Serum Albumin, Human