Anti-heat shock protein autoantibody profiling in breast cancer using customized protein microarray

Abstract

Heat shock proteins (HSPs) are over-expressed in a wide range of human cancers. It results in the stimulation of the immune system and consequently in elevated concentration of anti-HSP autoantibodies. Elevated anti-HSP autoantibodies were found in breast cancer patients, and they are associated with tumor metastasis. Therefore, screening these autoantibodies could be of diagnostic and prognostic values. Protein microarrays have already demonstrated their great potential as a diagnostic tool. However, protein diversity requires optimization of the microarray fabrication to achieve high sensitivity and specificity. In this study, seven HSPs were immobilized on six different surface chemistries. After evaluation and optimization with purified antibodies of the six surface chemistries, two surfaces were selected to detect anti-HSP autoantibodies in breast cancer sera. Multiplex detection of anti-HSP autoantibodies allowed discrimination of breast cancer patients (50) from healthy controls (26) with a sensitivity of 86% and a specificity of 100%.

A comprehensive autoantigen-ome of autoimmune liver diseases identified from dermatan sulfate affinity enrichment of liver tissue proteins

“…Autoantibodies to heat shock proteins (HSP) are widely found in autoimmune diseases as well as in numerous other diseases. Autoantibodies to HSP have been found in the circulation of various cancer patients, and are proposed as diagnostic and prognostic markers for various cancers such as breast cancer [40]. Autoantibodies to Glud1 have not been reported in humans but in mice and calves [27, 28].…”

Challenges and Opportunities in Clinical Applications of Blood-Based Proteomics in Cancer

“…For example, a set of 10 potential BCa serum biomarkers and cancer antigens (haptoglobin, osteopontin (OPN), CA15-3, CA125, carbohydrate antigen 19-9 (CA19-9), CEA, prolactin, α-fetoprotein (AFP), leptin, and migration inhibitory factor (MIF)) were developed for diagnosis and screening, but none of them are detected to have a high specificity, particularly in detecting early stage disease [ 176 , 177 ]. Other plasma candidate biomarkers available used for the screening and diagnosis of BCa include serpin peptidase inhibitor (SERPINB4), secreted-clusterin (CLU), serum amyloid (SAA), and heat shock proteins (HSPs) [ 128 , 129 , 178 , 179 ], but have yet to be validated in large studies for population application strategies. The majority of the markers reported by single breast cancer studies are based on a limited number of samples, hence the validation of biomarker candidates by the targeted profiling analysis of large cohorts of samples and populations is crucial for implementing those in clinical application.…”

Autoantibodies as biomarkers for breast cancer diagnosis and prognosis

“…The analysis of p53 autoantibody levels is helpful for breast cancer screening, but because of the relatively low sensitivity, its efficacy is not ideal. However, in recent years there have been several studies using panels including p53 autoantibody, which have yielded high specificities as well as high sensitivities ( 53 , 75 ). P53 and its autoantibody are widely detected to exist in tissues or serum of different kinds of cancer, and there are no studies on the specificity of p53 autoantibody in breast cancer patients so far.…”

“…combined the classic biomarker CA 15-3 with FTH1 and hnRNPF autoantibodies into a panel and yielded a sensitivity of 89.3% and a specificity of 93.8% ( 108 ). A combination of multiple HSP and p53 autoantibodies yielded a sensitivity of 86% and a specificity of 100% ( 53 ). Although it is hard to do accurate mathematical statistics, we can see from Table 1 that generally speaking, studies using panels have yielded a higher area under the ROC curve (AUC) and higher sensitivity, while the specificity does not seem to have been improved by panels ( Table 1 and Figure 2 ).…”