SAN FRANCISCOHaptoglobin-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
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.