Immunosignaturing Can Detect Products from Molecular Markers in Brain Cancer

Abstract

Immunosignaturing shows promise as a general approach to diagnosis. It has been shown to detect immunological signs of infection early during the course of disease and to distinguish Alzheimer’s disease from healthy controls. Here we test whether immunosignatures correspond to clinical classifications of disease using samples from people with brain tumors. Blood samples from patients undergoing craniotomies for therapeutically naïve brain tumors with diagnoses of astrocytoma (23 samples), Glioblastoma multiforme (22 samples), mixed oligodendroglioma/astrocytoma (16 samples), oligodendroglioma (18 samples), and 34 otherwise healthy controls were tested by immunosignature. Because samples were taken prior to adjuvant therapy, they are unlikely to be perturbed by non-cancer related affects. The immunosignaturing platform distinguished not only brain cancer from controls, but also pathologically important features about the tumor including type, grade, and the presence or absence of O6-methyl-guanine-DNA methyltransferase methylation promoter (MGMT), an important biomarker that predicts response to temozolomide in Glioblastoma multiformae patients.

General Assessment of Humoral Activity in Healthy Humans

“…Immunosignaturing is well-suited for detection and classification of diseases and vaccines (4,5,(22)(23)(24)(25)(26). In each of these demonstrations, there were controls representing an "unaffected" state, but the clinical definition of unaffected varied by researcher.…”

Scalable high-density peptide arrays for comprehensive health monitoring

“…The blood is diluted with little or no additional processing and incubated with a large array of different nonnatural-sequence peptides (reviewed in Sykes et al 9 ). Our initial platform was an array of 10,000 presynthesized peptides spotted on a glass slide, and we have used this format to characterize immune responses to vaccines 10 , infectious diseases 11 , cancer 12,13 , Alzheimer's Disease 14 and autoimmune disorders 12 . The work on brain cancer 13 was performed as a blinded train/test study, training on a patient cohort taken in 2007 and testing on a cohort from 2010, with 100% accuracy of identification.…”

“…Our initial platform was an array of 10,000 presynthesized peptides spotted on a glass slide, and we have used this format to characterize immune responses to vaccines 10 , infectious diseases 11 , cancer 12,13 , Alzheimer's Disease 14 and autoimmune disorders 12 . The work on brain cancer 13 was performed as a blinded train/test study, training on a patient cohort taken in 2007 and testing on a cohort from 2010, with 100% accuracy of identification. We have also shown that it is feasible to detect signatures before the onset of symptoms in mouse models 15 and in human pre-pancreatic cancer samples 12 .…”

Immunosignature system for diagnosis of cancer

“…To meet this objective, independent signatures for multiple diseases would be obtained from the same array. We had previously demonstrated that the same array could signature infections (15), Alzheimer's disease (31,32), pancreatic diseases (16), and four types of brain cancer (19). However, in trial 2, we significantly expanded the demand for cross-disease distinction.…”

“…The goal of the current work is to test the multidisease aspect of immunosignatures rigorously. Although the approach has previously been used to discriminate various subtypes of brain cancer (19), it has not yet demonstrated multiplexed cancer diagnosis. Here, we perform a blinded train/test validation study wherein a group of 120 individuals with five different cancers from various geographic regions was used as a training set to define a multicancer signature.…”