Serum biomarkers for detection of breast cancers: a prospective study
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Using surface-enhanced laser desorption/ionization-time of flight (SELDI-TOF), Li et al. [Clin Chem 48(8): 1296–1304, 2002] identified 3 serum biomarkers, BC1 (4.3 kDa), BC2 (8.1 kDa) and BC3 (8.9 kDa), whose combination significantly detects breast cancer patients from non-cancer controls. This work aimed to validate these biomarkers in an independent prospective study. We screened 89 serum samples including 49 breast cancers at pT1-4N0M0 (n = 23), pT1-4N1-3M0 (n = 17) or pT1-4N0-3M1 (n = 9) stages, 13 benign breast diseases and 27 healthy women. The BC2 biomarker significance was not recovered. However, we found 2 peaks that we named BC1a (4286 Da) and BC1b (4302 Da), that could correspond to Li’s BC1 since they significantly decrease in breast cancers (p < 0.00007 and p < 0.0002, respectively). Similarly, BC3a (8919 Da) and BC3b (8961 Da) are significantly increased in breast cancers (p < 0.02 and p < 0.0002, respectively) and could correspond to the Li’s BC3. For each biomarker we defined stringent (no errors) and flexible (less than 10% errors) cut-off values and tested the power of the combined BC1a/BC1b/BC3a/BC3b stringent and flexible profiles to discriminate breast cancers. They identified 33% and 45% cancers, respectively. Applied to the same series, Ca 15.3 test identified 22% patients. Interestingly, in association with the BC1a/BC1b/BC3a/BC3b profiles, Ca 15.3 improved the number of detected cancers indicating that it is an independent parameter. Collectively, our data partially validate those of Li’s study and confirm that the BC1 and BC3 biomarkers are helpful for breast cancer diagnosis.
Keywordsbreast cancer prospective study proteomics SELDI-TOF serum biomarkers
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We thank Kadour Annane, Sophie Bayer, Jean-Pierre Bellocq, Jean-Pierre Bergerat, Jean-Philippe Brettes, Marie-Pierre Chenard, Patrick Dufour, Françoise Eichler, Michèle Grima, Sandrine Kandel, Emmanuel Kurtz, Jean-Louis Mehl and Gabrielle Tagland for their collaboration, and Susan Chan for her helpful discussion. This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, the Hôpital Universitaire de Strasbourg, the Association pour la Recherche sur le Cancer, and the European Commission (FP5 QLK3-CT-2002-02136, FP6 LSHC-CT-2003-503297), and Novartis. We are indebted to the Ligue Nationale Française contre le Cancer and the Comités du Haut-Rhin et du Bas-Rhin for their constant and considerable financial support. A.C. was a recipient of a Centre Anti-Cancéreux Paul Strauss fellowship.
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