Seromic profiling of ovarian and pancreatic cancer.
Autoantibodies, a hallmark of both autoimmunity and cancer, represent an easily accessible surrogate for measuring adaptive immune responses to cancer. Sera can now be assayed for reactivity against thousands of proteins using microarrays, but there is no agreed-upon standard to analyze results. We developed a set of tailored quality control and normalization procedures based on ELISA validation to allow patient comparisons and determination of individual cutoffs for specificity and sensitivity. Sera from 60 patients with pancreatic cancer, 51 patients with ovarian cancer, and 53 age-matched healthy donors were used to assess the binding of IgG antibodies against a panel of >8000 human antigens using protein microarrays and fluorescence detection. The resulting data interpretation led to the definition and ranking of proteins with preferred recognition by the sera from cancer patients in comparison with healthy donors, both by frequency and strength of signal. We found that 202 proteins were preferentially immunogenic in ovarian cancer sera compared to 29 in pancreatic cancer, with few overlaps. Correlates of autoantibody signatures with known tumor expression of corresponding antigens, functional pathways, clinical stage, and outcome were examined. Serological analysis of arrays displaying the complete human proteome (seromics) represents a new era in cancer immunology, opening the way to defining the repertoire of the humoral immune response to cancer.
Gnjatic
Sacha
S
Ludwig Institute for Cancer Research Ltd, Memorial-Sloan Kettering Cancer Center, New York, NY 10065, USA. gnjatics@mskcc.org
Ritter
Erika
E
Büchler
Markus W
MW
Giese
Nathalia A
NA
Brors
Benedikt
B
Frei
Claudia
C
Murray
Anne
A
Halama
Niels
N
Zörnig
Inka
I
Chen
Yao-Tseng
YT
Andrews
Christopher
C
Ritter
Gerd
G
Old
Lloyd J
LJ
Odunsi
Kunle
K
Jäger
Dirk
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D014408:Biomarkers, Tumor / Q000276:immunology; D001782:Blood Donors; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D052138:Genes, Neoplasm; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000097:blood; D010051:Ovarian Neoplasms / Q000097:blood* / Q000235:genetics / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000235:genetics / Q000276:immunology; D040081:Protein Array Analysis / Q000379:methods*; D020543:Proteome / Q000378:metabolism*; D015203:Reproducibility of Results
D001323:Autoantibodies; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D020543:Proteome