Serum S100A6 concentration predicts peritoneal tumor burden in mice with epithelial ovarian cancer and is associated with advanced stage in patients.
BACKGROUND
Ovarian cancer is the 5th leading cause of cancer related deaths in women. Five-year survival rates for early stage disease are greater than 94%, however most women are diagnosed in advanced stage with 5 year survival less than 28%. Improved means for early detection and reliable patient monitoring are needed to increase survival.


RESULTS
Applying mass spectrometry-based proteomics, we sought to elucidate an unanswered biomarker research question regarding ability to determine tumor burden detectable by an ovarian cancer biomarker protein emanating directly from the tumor cells. Since aggressive serous epithelial ovarian cancers account for most mortality, a xenograft model using human SKOV-3 serous ovarian cancer cells was established to model progression to disseminated carcinomatosis. Using a method for low molecular weight protein enrichment, followed by liquid chromatography and mass spectrometry analysis, a human-specific peptide sequence of S100A6 was identified in sera from mice with advanced-stage experimental ovarian carcinoma. S100A6 expression was documented in cancer xenografts as well as from ovarian cancer patient tissues. Longitudinal study revealed that serum S100A6 concentration is directly related to tumor burden predictions from an inverse regression calibration analysis of data obtained from a detergent-supplemented antigen capture immunoassay and whole-animal bioluminescent optical imaging. The result from the animal model was confirmed in human clinical material as S100A6 was found to be significantly elevated in the sera from women with advanced stage ovarian cancer compared to those with early stage disease.


CONCLUSIONS
S100A6 is expressed in ovarian and other cancer tissues, but has not been documented previously in ovarian cancer disease sera. S100A6 is found in serum in concentrations that correlate with experimental tumor burden and with clinical disease stage. The data signify that S100A6 may prove useful in detecting and/or monitoring ovarian cancer, when used in concert with other biomarkers.
Wei
Bih-Rong
BR
Molecular Pathology Unit, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
Hoover
Shelley B
SB
Ross
Mark M
MM
Zhou
Weidong
W
Meani
Francesco
F
Edwards
Jennifer B
JB
Spehalski
Elizabeth I
EI
Risinger
John I
JI
Alvord
W Gregory
WG
Quiñones
Octavio A
OA
Belluco
Claudio
C
Martella
Luca
L
Campagnutta
Elio
E
Ravaggi
Antonella
A
Dai
Ren-Ming
RM
Goldsmith
Paul K
PK
Woolard
Kevin D
KD
Pecorelli
Sergio
S
Liotta
Lance A
LA
Petricoin
Emanuel F
EF
Simpson
R Mark
RM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins / Q000097:blood*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics*; D040901:Proteomics / Q000379:methods*; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000097:blood*
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C489134:S100a6 protein, mouse; C055351:S100A6 protein, human