Haptoglobin-Alpha, Potential Marker for Ovarian Cancer, Identified

SAN FRANCISCO—Haptoglobin-alpha, a subunit of the hemoglobin-binding protein haptoglobin, may be a useful marker for ovarian cancer, according to results presented at the 93rd Annual Meeting of the American Association for Cancer Research (abstract 3687).

Researchers from the Laboratory of Gynecologic Oncology at Brigham and Women’s Hospital and Harvard Medical School used four varieties of surface-specific ProteinChip arrays (Ciphergen Biosystems Inc.) to screen for smaller proteins (less than 50 kDa) that could potentially be used as markers for ovarian cancer.

Surface enhanced laser desorption/ionization (SELDI)-mass spectroscopy analysis of serum samples from 58 women who had ovarian cancer and 50 controls revealed several protein peaks, including a protein peak at approximately 11,700 Da using the copper surface (IMAC3) chip. Following purification by affinity chromatography and sequencing by Ion Trap Tandem Mass Spectrometry, the protein was identified as haptoglobin-alpha.

"Interestingly, this protein was previously identified about 15 years ago and was correlated with ovarian cancer," said Bin Ye, PhD, a postdoctoral research fellow at Harvard Medical School.

Haptoglobin consists of beta and alpha subunits. The alpha chain of haptoglobin was found in all of the common histologic subtypes of epithelial ovarian cancer. Specificity and sensitivity of haptoglobin-alpha for ovarian cancer were 70% and 83%, respectively, when it was present at a concentration intensity of more than 0.2 from the SELDI output.

The researchers then developed an antibody to haptoglobin-alpha. Using this purified polyclonal antibody, the ELISA screening test of serum from 94 women with ovarian cancer and 99 controls demonstrated specificity and sensitivity of 83% and 82%, respectively.

Increased glycosylation of haptoglobin was observed in the women with ovarian cancer, "but we have no data to show that haptoglobin-alpha is formed by this mechanism," Dr. Ye said.

Their research has not yet determined whether glycosylation occurs in the tumor or elsewhere in the body, or why ovarian cancer would stimulate this process. Haptoglobin is made in the liver and prevents iron loss by binding to hemoglobin. It is not yet clear why ovarian cancer would have any effect on this serum protein.

"This is just the first step, using protein chip technology to identify serum markers," Dr. Ye said. "We’re still working on this, and we are working to identify a few other markers as well. "