Pattern of Serum Autoantibodies Allows Accurate Distinction between a Tumor and Pathologies of the Same Organ

Purpose: Recent studies impressively showed the diagnostic potential of seroreactivity patterns for different tumor types, offering the prospect for low-cost screening of numerous tumor types simultaneously. One of the major challenges toward this goal is to prove that seroreactivity profiles do not only allow for identifying a tumor but also allow for distinguishing tumors from other pathologies of the same organ. Experimental Design: We chose glioma as a model system and tested 325 sera (88 glioma, 95 intracranial tumors, 60 other brain pathologies, and 82 healthy controls) for seroreactivity on a panel of 35 antigens. Results: We were able to discriminate between glioma and all other sera with cross-validated specificity of 86.1%, sensitivity of 85.2%, and accuracy of 85.8%. We obtained comparably good results for the separation of glioma versus nontumor brain pathologies and glioma versus other intracranial tumors. Conclusion: Our study provides first evidence that seroreactivity patterns allow for an accurate discrimination between a tumor and pathologies of the same organ even between different tumor types of the same organ.

[1]  Robert E. Lewis,et al.  Ras regulates assembly of mitogenic signalling complexes through the effector protein IMP , 2004, Nature.

[2]  J. Bonnin,et al.  Immunohistochemistry of central nervous system tumors. Its contributions to neurosurgical diagnosis. , 1984, Journal of neurosurgery.

[3]  Christina Backes,et al.  Complex humoral immune response against a benign tumor: frequent antibody response against specific antigens as diagnostic targets. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Masahiro Toda,et al.  Identification of a human glioma antigen, SOX6, recognized by patients' sera , 2004, Oncogene.

[5]  Sang Joon Kim,et al.  A Mathematical Theory of Communication , 2006 .

[6]  Thierry Boon,et al.  Tumor‐specific shared antigenic peptides recognized by human T cells , 2002, Immunological reviews.

[7]  Debashis Ghosh,et al.  Autoantibody signatures in prostate cancer. , 2005, The New England journal of medicine.

[8]  M J O'Hare,et al.  Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression. , 2001, Cancer immunity.

[9]  M. Pfreundschuh,et al.  Human neoplasms elicit multiple specific immune responses in the autologous host. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[10]  J. Roder,et al.  A cyclophilin-related protein involved in the function of natural killer cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[11]  A. Benabid,et al.  Antibodies to endostatin in a multifocal glioblastoma patient , 2000, The Lancet.

[12]  W Feiden,et al.  PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme , 2001, Oncogene.

[13]  U. Fischer,et al.  cDNA cloning and chromosomal mapping of a predicted coiled-coil proline-rich protein immunogenic in meningioma patients. , 1997, Human molecular genetics.

[14]  Brad Stone,et al.  Application of Bayesian modeling of autologous antibody responses against ovarian tumor-associated antigens to cancer detection. , 2006, Cancer research.

[15]  U. Fischer,et al.  Autoantibodies against GLEA2 and PHF3 in glioblastoma: Tumor‐associated autoantibodies correlated with prolonged survival , 2005, International journal of cancer.

[16]  A. Söling,et al.  Minichromosome maintenance protein 3 elicits a cancer-restricted immune response in patients with brain malignancies and is a strong independent predictor of survival in patients with anaplastic astrocytoma. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  M. Pfreundschuh,et al.  Analysis of the antibody repertoire of astrocytoma patients against antigens expressed by gliomas , 2002, International journal of cancer.

[18]  P. Walker,et al.  Immunobiology of Gliomas: New Perspectives for Therapy a , 1997, Annals of the New York Academy of Sciences.

[19]  Weiliang Qiu,et al.  Development of a “reverse capture” autoantibody microarray for studies of antigen‐autoantibody profiling , 2006, Proteomics.

[20]  U. Fischer,et al.  Glioma‐expressed antigen 2 (GLEA2): a novel protein that can elicit immune responses in glioblastoma patients and some controls , 2001, Clinical and experimental immunology.

[21]  Arnold J Stromberg,et al.  Using protein microarray as a diagnostic assay for non-small cell lung cancer. , 2005, American journal of respiratory and critical care medicine.

[22]  H. Himmelbauer,et al.  An endoribonuclease-prepared siRNA screen in human cells identifies genes essential for cell division , 2004, Nature.

[23]  Eckart Meese,et al.  SePaCS—a web-based application for classification of seroreactivity profiles , 2007, Nucleic Acids Res..

[24]  C. Chow,et al.  Expression of MAGE and GAGE in high-grade brain tumors: a potential target for specific immunotherapy and diagnostic markers. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[25]  Eckart Meese,et al.  A minimally invasive multiple marker approach allows highly efficient detection of meningioma tumors , 2006, BMC Bioinformatics.

[26]  F. Wilcoxon Individual Comparisons by Ranking Methods , 1945 .

[27]  W. Mandemakers,et al.  The neurite outgrowth inhibitor Nogo A is involved in autoimmune-mediated demyelination , 2004, Nature Neuroscience.

[28]  D. Ghosh,et al.  Autoantibody profiles reveal ubiquilin 1 as a humoral immune response target in lung adenocarcinoma. , 2007, Cancer research.

[29]  Gerard Tromp,et al.  Diagnostic markers of ovarian cancer by high-throughput antigen cloning and detection on arrays. , 2006, Cancer research.

[30]  H. B. Mann,et al.  On a Test of Whether one of Two Random Variables is Stochastically Larger than the Other , 1947 .