title: Analysis of acute-phase proteins, AHSG, C3, CLI, HP and SAA, reveals distinctive expression patterns associated with breast, colorectal and lung cancer.
abstract: Early detection, clinical management and disease recurrence monitoring are critical areas in cancer treatment in which specific biomarker panels are likely to be very important in each of these key areas. We have previously demonstrated that levels of alpha-2-heremans-schmid-glycoprotein (AHSG), complement component C3 (C3), clusterin (CLI), haptoglobin (HP) and serum amyloid A (SAA) are significantly altered in serum from patients with squamous cell carcinoma of the lung. Here, we report the abundance levels for these proteins in serum samples from patients with advanced breast cancer, colorectal cancer (CRC) and lung cancer compared to healthy controls (age and gender matched) using commercially available enzyme-linked immunosorbent assay kits. Logistic regression (LR) models were fitted to the resulting data, and the classification ability of the proteins was evaluated using receiver-operating characteristic curve and leave-one-out cross-validation (LOOCV). The most accurate individual candidate biomarkers were C3 for breast cancer [area under the curve (AUC) = 0.89, LOOCV = 73%], CLI for CRC (AUC = 0.98, LOOCV = 90%), HP for small cell lung carcinoma (AUC = 0.97, LOOCV = 88%), C3 for lung adenocarcinoma (AUC = 0.94, LOOCV = 89%) and HP for squamous cell carcinoma of the lung (AUC = 0.94, LOOCV = 87%). The best dual combination of biomarkers using LR analysis were found to be AHSG + C3 (AUC = 0.91, LOOCV = 83%) for breast cancer, CLI + HP (AUC = 0.98, LOOCV = 92%) for CRC, C3 + SAA (AUC = 0.97, LOOCV = 91%) for small cell lung carcinoma and HP + SAA for both adenocarcinoma (AUC = 0.98, LOOCV = 96%) and squamous cell carcinoma of the lung (AUC = 0.98, LOOCV = 84%). The high AUC values reported here indicated that these candidate biomarkers have the potential to discriminate accurately between control and cancer groups both individually and in combination with other proteins.
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Dublin 9, Ireland. paul.dowling@dcu.ie
authors.forename: Paul
authors.initials: P
authors.lastname: Dowling
authors.forename: Colin
authors.initials: C
authors.lastname: Clarke
authors.forename: Kim
authors.initials: K
authors.lastname: Hennessy
authors.forename: Beatriz
authors.initials: B
authors.lastname: Torralbo-Lopez
authors.forename: Jo
authors.initials: J
authors.lastname: Ballot
authors.forename: John
authors.initials: J
authors.lastname: Crown
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kiernan
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: O'Byrne
authors.forename: M John
authors.initials: MJ
authors.lastname: Kennedy
authors.forename: Vincent
authors.initials: V
authors.lastname: Lynch
authors.forename: Martin
authors.initials: M
authors.lastname: Clynes
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000378:metabolism*; D051152:Clusterin / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006242:Haptoglobins / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D000685:Serum Amyloid A Protein / Q000378:metabolism; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism
chemical_list: C556354:AHSG protein, human; D000209:Acute-Phase Proteins; D014408:Biomarkers, Tumor; C495242:CLU protein, human; D051152:Clusterin; D003176:Complement C3; D006242:Haptoglobins; D000685:Serum Amyloid A Protein; D060749:alpha-2-HS-Glycoprotein