Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery

Qian Shi, Lyndsay N. Harris, Xin Lu, Xiaochun Li, Justin Hwang, Robert Gentleman, J. Dirk Iglehart, Alexander Miron

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 indicateded 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.

Original languageEnglish (US)
Pages (from-to)2947-2955
Number of pages9
JournalJournal of Proteome Research
Volume5
Issue number11
DOIs
StatePublished - Nov 2006
Externally publishedYes

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Biomarkers
Fibrinogen
Surgery
Breast Neoplasms
Plasmas
Optical resolving power
Robotics
Tumor Biomarkers
Routine Diagnostic Tests
ROC Curve
Area Under Curve
Ionization
Longitudinal Studies
Desorption
Mass Spectrometry
Neoplasms
Screening
Lasers
Blood
Spectroscopy

Keywords

  • Breast cancer
  • Fibrinogen
  • HER2
  • Plasma
  • Proteomics

ASJC Scopus subject areas

  • Genetics
  • Biotechnology
  • Biochemistry

Cite this

Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery. / Shi, Qian; Harris, Lyndsay N.; Lu, Xin; Li, Xiaochun; Hwang, Justin; Gentleman, Robert; Iglehart, J. Dirk; Miron, Alexander.

In: Journal of Proteome Research, Vol. 5, No. 11, 11.2006, p. 2947-2955.

Research output: Contribution to journalArticle

Shi, Qian ; Harris, Lyndsay N. ; Lu, Xin ; Li, Xiaochun ; Hwang, Justin ; Gentleman, Robert ; Iglehart, J. Dirk ; Miron, Alexander. / Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery. In: Journal of Proteome Research. 2006 ; Vol. 5, No. 11. pp. 2947-2955.
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