Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients.
OBJECTIVE
To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer (OC) patients.


METHODS
Serum from 150 OC patients was tested using SELDI-TOF-MS.


RESULTS
A proteomic prognostic index (xb-pro) was constructed using the regression coefficients based on inter-α trypsin IV internal fragment, B2M and TT. A multivariable Cox survival analysis including the xb-pro index showed that xb-pro (p<0.0001, HR=2.50, 95% CI: 1.65-3.79), residual tumor after primary surgery (p=0.0005), age (p=0.01) and chemotherapy (p=0.0002) are of independent prognostic value for overall survival. International Federation of Gynecology and Obstetrics stage, performance status, histological type of tumor and serum CA125 were found of no independent value. A proteomic index (xb-pfs) based on B2M and CTAP3 was found to predict progression-free survival (xb-pfs: p=0.008, HR=1.77, 95% CI: 1.17-2.70 together with type of surgery, age and chemotherapy.


CONCLUSIONS
We found an index with three proteomic biomarkers (xb-pro) to be of independent prognostic value for overall survival and an index with two proteomic biomarkers (xb-pfs) with evidence of independent prognostic value for progression-free survival.
Department of Pathology, Danish CancerBiobank, Herlev University Hospital, Copenhagen, Denmark. Hogdall@dadlnet.dk
Estrid
E
Høgdall
Eric T
ET
Fung
Ib Jarle
IJ
Christensen
Christine
C
Yip
Lotte
L
Nedergaard
Svend Aage
SA
Engelholm
Signe
S
Risum
Anette Lykke
AL
Petri
Lene
L
Lundvall
Lee
L
Lomas
Claus
C
Høgdall
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001798:Blood Proteins; D018394:CA-125 Antigen / Q000097:blood; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000473:pathology*; D010455:Peptides / Q000097:blood; D011228:Prealbumin / Q000032:analysis; D011379:Prognosis; D011446:Prospective Studies; D040081:Protein Array Analysis; D053491:Proteinase Inhibitory Proteins, Secretory / Q000097:blood; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D016019:Survival Analysis; D001613:beta 2-Microglobulin / Q000097:blood
D014408:Biomarkers, Tumor; D001798:Blood Proteins; D018394:CA-125 Antigen; D006023:Glycoproteins; C091236:ITIH4 protein, human; D010455:Peptides; D011228:Prealbumin; D053491:Proteinase Inhibitory Proteins, Secretory; D001613:beta 2-Microglobulin; C009862:connective tissue-activating peptide