Early detection remains the most promising approach to improve long-term survival of patients with
ovarian cancer. In a five-center case-control study, serum proteomic expressions were analyzed on 153 patients with invasive
epithelial ovarian cancer, 42 with other
ovarian cancers, 166 with benign pelvic masses, and 142 healthy women. Data from patients with early stage
ovarian cancer and healthy women at two centers were analyzed independently and the results cross-validated to discover potential
biomarkers. The results were validated using the samples from two of the remaining centers. After
protein identification,
biomarkers for which an immunoassay was available were tested on samples from the fifth center, which included 41 healthy women, 41 patients with
ovarian cancer, and 20 each with breast, colon, and
prostate cancers. Three
biomarkers were identified as follows: (a)
apolipoprotein A1 (down-regulated in
cancer); (b) a truncated form of
transthyretin (down-regulated); and (c) a cleavage fragment of
inter-alpha-trypsin inhibitor heavy chain H4 (up-regulated). In independent validation to detect early stage invasive
epithelial ovarian cancer from healthy controls, the sensitivity of a multivariate model combining the three
biomarkers and CA125 [74% (95% CI, 52-90%)] was higher than that of CA125 alone [65% (95% CI, 43-84%)] at a matched specificity of 97% (95% CI, 89-100%). When compared at a fixed sensitivity of 83% (95% CI, 61-95%), the specificity of the model [94% (95% CI, 85-98%)] was significantly better than that of CA125 alone [52% (95% CI, 39-65%)]. These
biomarkers demonstrated the potential to improve the detection of early stage
ovarian cancer.