Autoantibodies as cancer biomarkers

18 February 2010

Identifying cancers early requires the early identification of cancer biomarkers such as elevated levels of tumour-specific proteins (antigens), such as analysis of prostate specific antigen (commonly known as PSA) for prostrate cancer or cancer antigen 125 for ovarian cancer. However, these molecules can be hard to detect in the early stages of cancer as their levels are too low and they may be broken down more quickly during this stage. An alternative strategy is to monitor antibodies produced against these cancer-specific antigens, as they are produced in greater numbers even when the amount of antigen is low, and circulate for longer in blood stream.

Antibodies are usually produced by the immune system to attack external (‘non-self’) antigens. However, autoantibodies target an individual’s own proteins and can be the cause of  diseases such as rheumatoid arthritis and type I diabetes. Autoantibodies are also produced in response to antigens on the surface of tumour cells; this may be at an early stage of carcinogenesis. One particular type of antigen which may elicit a response are glycoproteins (proteins with sugar molecules). In tumour cells, these molecules may be abnormally glycosylated, provoking an immune response – but it is a challenge to identify particular abnormal glycoproteins of this type. In a paper published in Cancer Research, Wandall et al. describe the development of a microarray system that can be used to analyze blood samples for the presence of specific autoantibodies directed against these abnormal glycoproteins [Wandall et al. (2009) Cancer Res: 70(4):1306-13].

Wandall et al. created a library of cancer-associated glycoproteins on a microarray platform. This library was then used to screen the blood of patients with ovarian, breast or prostate cancer (approximately 20 patients in each group) as well as healthy individuals. Autoantibodies were successfully detected in 30% of the patients and not in control samples, but none of them allowed sensitivity of detection high enough for clinical use as biomarkers.

This was because the pattern of glycosylation of proteins varies between cells, meaning that a large number of different, variable versions can be present in cancer cells, so that identification of specific variants that are elevated in cancer cells is a challenge. The authors propose that large glycopeptides arrays containing molecules synthesised in vitro could be a mechanism by which to investigate the abnormal glycoprotein expression patterns in specific cancers and may allow better targeted investigation of specific autoantibodies and ultimately earlier identification of cancer.

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