discovery case study
discovery case study
According to the American Cancer Society, prostate cancer is the most prevalent cancer in men, with more than 220,000 new cases and nearly 30,000 deaths in the United States in 2003. It is estimated that more than 35 million PSA tests are performed worldwide each year, and the market is expected to grow significantly in the future as the population ages.
PSA (Prostate Specific Antigen) is the world's most successful cancer diagnostic. With over $350 million in annual sales, PSA has enabled early screening of prostate cancer which has led to significant decline in the number of deaths in men afflicted with the disease. Financially, PSA sales represent 40% of all annual cancer serum biomarker revenues. The reason for its large market share is that currently it is the only cancer biomarker that is being used for mass-screening.
In recent years, the scientific community increasingly has questioned the accuracy of PSA screening, which was introduced 17 years ago and has significant limitations.
First, because the antigen is specific for prostate tissue, not prostate cancer, an elevated PSA does not always indicate prostate cancer. Only 25% of patients found to be positive (>4.0 ng/ml) by PSA screening will be confirmed by a biopsy to have cancer. As a result, urologists must decide whether to conduct another biopsy or additional PSA tests in pursuit of an adequate diagnosis, or to delay follow-up, potentially allowing an undiagnosed tumour to grow unchecked. Furthermore, many prostate cancer experts now advocate an even lower PSA threshold for biopsy in an effort to detect more cancers. This lower threshold, however, would significantly increase the number of expensive and uncomfortable biopsies, many of which would be negative.
Second, because not all prostate cancers release high levels of antigen into the blood, routine PSA screening often fails to detect clinically significant cancers. These "false negative" results can lead to delayed detection, which reduces the chance that treatment will be effective once the diagnosis has been made.
Sense Proteomic has developed a prostate cancer specific marker panel by screening for serum autoantibodies in diseased and normal banked samples as well as from patients with Benign Prostatic Hypertrophy (BPH), a non-cancerous disease whose symptoms include enlargement of the prostate. We used over 80 commercially-sourced serum samples which we ran on our arrays producing nearly 200,000 data points. As the sample data set below shows, the difference between antibody positive and antibody negative samples is easily detected:
We then carried out data analysis to define a marker panel of 10-15 auto-antigens that would allow us to distinguish between cancerous and non-cancerous samples. This involved various machine learning techniques and statistical methods. To determine the sensitivity and specificity of the panel, we tested it against a disjoint subset of the serum sample data.
Our final panel gives superior sensitivity and specificity to PSA when tested on a set of 29 samples.
Whilst we are very excited by this result, we recognise further validation needs to be carried out with a bigger sample cohort and so we are presently adding additional patients to our serum sample set to enable us to carry out a large-scale validation of our marker panel.