Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Abstract

Current diagnostic techniques used for the early detection of cancers are successful but subject to detection bias. A recent focus lies in the development of more accurate diagnostic tools. An increase in serologic autoantibody levels has been shown to precede the development of cancer disease symptoms. Therefore, autoantibody levels in patient blood serum have been proposed as diagnostic biomarkers for early-stage diagnosis of cancers. Their clinical application has, however, been hindered by low sensitivity, specificity, and low predictive value scores. These scores have been shown to improve when panels of multiple diagnostic autoantibody biomarkers are used. A five-marker biomarker panel has been shown to increase the sensitivity of prostate cancer diagnosis to 95% as compared with 12.2% for prostate-specific antigen alone. New potential biomarker panels were also discovered for lung, colon, and stomach cancer diagnosis with sensitivity of 76%, 65.4%, and 50.8%, respectively. Studies in breast and liver cancer, however, seem to favor single markers, namely a-2-HS-glycoprotein and des-g-carboxyprothrombin with sensitivities of 79% and 89% for the early detection of the cancers. The aim of this review is to discuss the relevance of autoantibodies in cancer diagnosis and to outline the current methodologies used in the detection of autoantibodies. The review concludes with a discussion of the autoantibodies currently used in the diagnosis of cancers of the prostate, breast, lung, colon, stomach, and liver. A discussion of the potential future use of autoantibodies as diagnostic cancer biomarkers is also included in this review. Cancer Epidemiol Biomarkers Prev; 22(12); 2161-81. Ó2013 AACR.

Alpha 2HS-glycoprotein, a tumor-associated antigen (TAA) detected in Mexican patients with early-stage breast cancer

“…However, these have been lacking in clinical usefulness because their sensitivity and specificity entertain values of < 70%, although many autoantigens may be detected by antibody-based methods and are considered candidates for oncogenic proteins [10,11,[20][21][22][23][24][25][26][29][30][31][32][33][34][35][38][39][40]. Validation of the most promising biomarkers proposed for the breast cancer diagnosis and prognosis has required the application of high evaluation standards in prospective cohort studies of women with breast cancer.…”

“…Therefore, the presence of the autoantibody and its levels in the patient's blood serum has been proposed as diagnostic biomarkers for early-stage diagnosis of cancer [9]. However, the presence of antibodies against these proteins have been observed in 15-30% of patients with breast cancer, and this led to the search for novel, better markers for the diagnosis of this pathology [10,11]. Immunoreactivity is caused by humoral immune responses, producing antigen-specific antibodies in the presence of tumor-associated antigens (TAA) that may be formed from different mechanisms, such as post-translational modifications or overexpressed protein with immunological relevance [12].…”

FOXP3 autoantibody as a potential early prognostic serum biomarker in patients with cervical cancer

“…Although these TAA autoantibodies vary among tumor types and among individuals, they are still potential diagnostic tumor biomarkers. In recent years, there has been much discussion regarding TAA autoantibodies as early tumor biomarkers to determine the therapeutic efficacy or evaluate disease prognosis [3,4]. While TAA expression level is low at the early cancer stage, they cannot be accurately detected by conventional protein detection methods; however, based on antigenantibody reaction, TAA autoantibodies could be detected with higher sensitivity.…”

A novel cohort of cancer-testis biomarker genes revealed through meta-analysis of clinical data sets.

“…This, in combination with the trend towards personalised approaches to cancer medicine means there is an increasing need to identify and develop cancer-specific biomarkers that can be employed in the development of early, pre-metastatic diagnostic and treatment strategies [1-7]. Additionally, advances in tumour immunology have reignited interest in cancer immunotherapeutics, such as cancer vaccines, adoptive therapeutics and targeted drug delivery using antibody-drug conjugates [8-17].…”