Analysis of the expression of human tumor antigens in ovarian cancer tissues.
Biomarkers for early detection of cancer have great clinical diagnostic potential. Numerous reports have documented the generation of humoral immune responses that are triggered in response to changes in protein expression patterns in tumor tissues and these biomarkers are referred to as tumor associated antigens (TAAs). Using a high-throughput technology, we previously identified 65 proteins as diagnostically useful TAAs by profiling the humoral immune responses in ovarian cancer (OVCA) patients. Here we determined the expression status of some of those TAAs in tissues from OVCA patients. The protein expression patterns of 4 of those 65 antigens, namely NASP, RCAS1, Nijmegen breakage syndrome1 (NBS1) and eIF5A, along with p53 and Her2 (known molecular prognosticators) and two proteins that interact with NBS1, MRE11 and RAD50, were assessed by immunohistochemistry (IHC). NASP and RCAS1 proteins were more frequently expressed in ovarian cancer tissues than with normal ovarian tissue and serous cystadenomas and MRE11 was less frequently expressed. When evaluated simultaneously, only NASP and MRE11 remained statistically significant with sensitivity of 66% and specificity of 89%. None of these proteins' expression levels were prognostic for survival. Together, our results indicate that occurrence of humoral immune responses against some of these TAAs in OVCA patients is triggered by antigen protein overexpression.
Ali-Fehmi
Rouba
R
Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Chatterjee
Madhumita
M
Ionan
Alexei
A
Levin
Nancy K
NK
Arabi
Haitham
H
Bandyopadhyay
Sudeshna
S
Shah
Jay P
JP
Bryant
Christopher S
CS
Hewitt
Stephen M
SM
O'Rand
Michael G
MG
Alekseev
Oleg M
OM
Morris
Robert
R
Munkarah
Adnan
A
Abrams
Judith
J
Tainsky
Michael A
MA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000096:biosynthesis; D001324:Autoantigens / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D018293:Cystadenoma, Serous / Q000175:diagnosis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D000076228:MRE11 Homologue Protein; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D046888:Tissue Array Analysis; D055815:Young Adult
D000951:Antigens, Neoplasm; D001324:Autoantigens; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C120762:EBAG9 protein, human; C121766:MRE11 protein, human; C489390:NASP protein, human; D009687:Nuclear Proteins; D000076228:MRE11 Homologue Protein