Promising results in ovarian cancer fight

Ciphergen Biosystems, from Fremont, CA, US, has helped in research which has led to the discovery of biomarkers and the development of a multi-marker pattern assay that shows promising results in the detection of early stage ovarian cancer.

The study, performed in collaboration with Ciphergen's Biomarker Discovery Center and the Johns Hopkins School of Medicine is published in Cancer Research. It describes the use of Ciphergen's ProteinChip System to discover three protein biomarkers that, when combined, form the basis of a clinical assay designed to detect stage I/II ovarian cancer. Each of the three proteins has been sequenced and identified with the use of the ProteinChip System; two of these novel biomarkers are cleaved products of precursor proteins and present in the serum at a fraction of the concentration of their corresponding full length proteins.

This study examined 503 patients and employed a multi-institutional study design, with both cross-validation and independent validation of the individual biomarkers as well as of the multi-marker pattern. The pattern of three biomarkers was able to diagnose early stage (I/II) ovarian cancer with 74% sensitivity at 97% specificity.

The study reported in Cancer Research utilised Ciphergen's SELDI-based ProteinChip System to generate protein expression profiles from serum obtained from 503 women with ovarian cancer, benign pelvic disease, or who were healthy. The samples were obtained from four hospitals, and a rigorous cross-validation and independent validation study design was employed. A sophisticated bioinformatics program was used to discover the three biomarkers and to generate a multi-marker pattern. The combined improvement in sensitivity and specificity is reflected in the higher area under the curve (AUC) of the receiver operator characteristic (ROC) for the three marker pattern (AUC = 92%). The study included purification and identification of the three markers, believed to be host response proteins, two of which had undergone post- translational modifications. The three markers were a processed form of ITIH4, a truncated form of transthyretin, and apolipoprotein A1.

Changes in transthyretin and apolipoprotein were independently validated in ovarian cancer samples from a fifth hospital using a traditional immunoassay. 'Because of the rigorous multi-institutional study design and the use of independent validation, we believe these results are more likely to be reproducible and therefore translated to clinical practice,' said Dr Robert Bast, vice-president of Translational Medicine at MD Anderson Cancer Center and co-author on the paper. 'Diagnosis of early stage ovarian cancer could play a critical role in decreasing the mortality from this disease. Ongoing work is being conducted to evaluate how these markers should be used in conjunction with other tests to achieve this goal.'

Approximately 23,000 new cases of ovarian cancer are diagnosed in the United States each year, and there are over 14,000 deaths from ovarian cancer each year. The high mortality is a result of the fact that most women are diagnosed with late stage ovarian cancer (III or IV). When ovarian cancer is diagnosed in its earlier stages (I or II), the cure rate approaches 80%. Therefore, a diagnostic test that can detect early stage ovarian cancer would be highly desirable. CA125, the only currently available tumor marker for ovarian cancer, has a sensitivity of approximately 30-50% for stage I/II ovarian cancer and is approved only for monitoring for recurrence after treatment.

'We are excited by these results and also to have licensed the test from Johns Hopkins in preparation for commercialisation,' stated Gail Page, president of Ciphergen's Diagnostics Division. 'We are currently validating these promising results in a 1500 sample trial and developing SELDI-based assays as part of our commercialisation strategy.'