Tumour‐Associated Autoantibodies as Diagnostic Biomarkers for Breast Cancer: A Systematic Review and Meta‐Analysis

Abstract

Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour-associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour-associated autoantibody was included in a meta-analysis, and its clinical value was determined using Fagan's nomogram. The analysis included 84 studies regarding tumour-associated autoantibodies with the diagnostic value. Anti-p53 antibody was the most frequently studied autoantibody, followed by autoantibodies against MUC1, HER2 and cyclin B1. Although individual tumour-associated autoantibodies showed low diagnostic sensitivity, combinations of autoantibodies offered relatively high sensitivity. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method, and nucleic acid programmable protein microarrays appeared preferable to common protein microarrays. As the most commonly studied autoantibody, anti-p53 antibody was included in a metaanalysis. When it had been detected using ELISA and cut-off values were defined as the mean +2 or 3 standard deviations, the summary area under the receiver operating characteristic curve for the presence of BC was 0.78. Fagan's nomogram showed post-test probabilities of 32% and 6% for positive and negative results, respectively. Mammography might be supplemented by the use of tumour-associated autoantibodies as biomarkers for BC diagnosis in younger women with increased risks of BC. Even though several studies have investigated the diagnostic use of tumour-associated autoantibodies as biomarkers for BC detection, a high-quality prospective study is needed to validate their diagnostic value in practice.

Rethinking Autoantibody Signature Panels for Cancer Diagnosis

“…The panels that have been developed to date do not have sufficient accuracy, and meta-analyses of autoantibody panels have found them to be lacking in sensitivity and specificity. 6,7 Recently, the EarlyCDT-Lung blood test (Oncimmune Ltd., Nottingham, United Kingdom) has been proposed to assess the risk for lung cancer. 8 This test is based on detection of seven autoantibodies.…”

Trial watch: DNA-based vaccines for oncological indications

“…The study demonstrated that recall vaccinations spaced by 1.5 months provide superior protection against tumor development as compared to vaccinations spaced by 3 or 6 months. Such a robust protective immunity was associated with improved production of ERBB2-specific antibodies 118 (and isotype switching to IgG2a), expansion of circulating CD4 C T cells, and increased cytotoxicity of ERBB2-specific cytotoxic T lymphocytes (CTLs) in vivo. 119 In another study, a plasmid encoding C-C motif chemokine ligand 4 (CCL4) [120][121][122] was co-administered with an ERBB2-coding construct in a mouse model of ERBB2 C cancer.…”

The crossroads between cancer immunity and autoimmunity antibodies to self antigens

“…Autoimmune disease and cancer patients have also been found to exhibit autoantibodies against MDM-2, which is the p53 inhibitor (33,34). Anti-c-Myc autoantibodies have been reported to occur in patients with gastric, breast, colon and ovarian cancer as well as in patients with SLE, Graves' disease, mixed connective tissue disease, dermatomyositis and autoimmune hemolytic anemia (5,27,(34)(35)(36)(37)(38)(39). Patients with colon, ovarian, breast and lung cancer as well as patients with SLE have been found to produce autoantibodies against the c-Myb protein (40).…”

“…Patients with colon, ovarian, breast and lung cancer as well as patients with SLE have been found to produce autoantibodies against the c-Myb protein (40). Both categories of patients generate autoantibodies against cyclin-B1, survivin, p16, 14-3-3 proteins, eukaryotic translation initiation factor 4G (eIF-4G) and RAF1 (14,27,28,(34)(35)(36)(40)(41)(42)(43)(44)(45)(46)(47)(48). Autoantibodies against the cyclic citrullinated peptide (CCP) were detected in patients with Sjogren's syndrome and psoriatic arthritis (51, 52) as well as in lymphoma patients (49).…”

“…© 1996-2017 in patients with osteosarcoma, HCC, breast, ovarian and other types of cancer (5,17,28,36,74,79,(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95). Autoantibodies against onconeural antigens, like Hu (ANNA-1) and Ri (ANNA-2) and against enzymes, like α-enolase, glutamate decarboxylase (GAD), tyrosinase, transglutaminase, carbonic anhydrase II (CAII), glyceraldehyde 3-phosphate dehydrogenase (GAP-DH), peroxiredoxin, superoxide dismutase (SOD) and coagulation factor XIII, have been reported in both patients with autoimmune diseases and cancer (5, 14,36,40,55,56,60,87,. Circulating autoantibodies against the ribosomal P proteins (P0, P1 and P2) are directed mainly to the carboxy-terminal epitope common to all three proteins and have been identified for the first time in SLE patients.…”