title: Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery.
abstract: Breast cancer is the most common nonskin malignancy affecting women. Currently, no simple, blood-based diagnostic test exists to complement radiological screening and increase sensitivity of detection. To screen plasma specimens and identify biomarkers that detect HER2-positive breast cancer, automated robotic sample processing followed by surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectroscopy was used. Multiple statistical algorithms were used to select biomarkers that segregate cancer patients versus controls and produced average CV rates ranging from 20% to 29%. A set of seven biomarkers were validated on an independent test data set and achieved the best error rate of 19.1%. A permutation test indicated a p-value for CV error less than 0.002. Moreover, a ROC curve using these biomarkers achieved an area-under-the-curve value of 0.95 on an independent test data set. The marker responsible for most of the resolving power was identified as a fragment of Fibrinogen Alpha (FGA) encompassing residues 605-629. This marker was present at lower levels in cancer patients as compared to controls. The importance of this biomarker was validated in a longitudinal study comparing pre- and post-operative levels and was shown to revert to normal levels after surgery. This fragment may serve as a useful diagnostic and treatment-monitoring marker.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shi
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Li
authors.forename: Justin
authors.initials: J
authors.lastname: Hwang
authors.forename: Robert
authors.initials: R
authors.lastname: Gentleman
authors.forename: J Dirk
authors.initials: JD
authors.lastname: Iglehart
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
mesh_terms: D000595:Amino Acid Sequence; D001331:Automation; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000601:surgery*; D005189:False Positive Reactions; D005260:Female; D005340:Fibrinogen / Q000737:chemistry*; D006801:Humans; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D040081:Protein Array Analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000235:genetics; D012016:Reference Values; D015203:Reproducibility of Results; D012371:Robotics
chemical_list: D014408:Biomarkers, Tumor; D005340:Fibrinogen; D010446:Peptide Fragments; D018719:Erb-b2 Receptor Tyrosine Kinases