title: Serpin b3 is associated with poor survival after chemotherapy and is a potential novel predictive biomarker in advanced non-small-cell lung cancer.
abstract: BACKGROUND
  In a previous biomarker discovery project using gene-expression profiling we identified Serpin B3 (SB3) as a predictor of resistance to platinum doublet chemotherapy (PtC) in non-small-cell lung cancer (NSCLC). This independent prospective study was designed to confirm the predictive utility of SB3.
  
  
  METHODS
  SB3 immunohistochemistry was scored by previously validated criteria (score 0 = negative, score 1 = 1%-10% tumor cells positive, score 2 = 11%-50% tumor cells positive, and score 3 = >50% tumor cell positive) in 197 patients with stage IV NSCLC treated with PtC. This provided 80% power to detect a median survival increase from 150 days in patients with an SB3 immunohistochemistry score of 2 or more to 300 days in those with an SB3 score of 0 or 1.
  
  
  RESULTS
  Thirty-six percent of NSCLCs stained positive for SB3. Median survival for SB3 negative/score 0 was 332 days, SB3 positive/score 1 was 268 days, and SB3 positive/score 2 or 3 was 120 days (p = 0.004). Cox proportional hazards analysis demonstrated that SB3 positivity is an independent predictor of survival (hazard ratio = 1.87; 95% confidence interval, 1.29-2.71; p = 0.001).The disease control rate in SB3 score 0, 1 = 65%, and score of 2 or more = 20 % (p = 0.002), with median survival 306 days (score 0, 1) versus 120 days (score ≥ 2, hazard ratio= 1.71; 95% confidence interval. 1.14-3.10; p = 0.002).
  
  
  CONCLUSIONS
  SB3-positive immunohistochemistry score of 2 or more (>10% tumor cells positive) identifies a subgroup of patients with stage IV NSCLC who have a poor survival (median 120 days) when treated with PtC, similar to that estimated for untreated or chemo-refractory stage IV NSCLC. Further prospective qualification using biospecimens from randomized studies is needed, but SB3 seems to be a useful biomarker that identifies a highly resistant subgroup in whom PtC should be avoided.
authors.affiliation: *School of Medicine and Dentistry, University of Aberdeen, Foresterhill Healthcare Campus, Foresterhill, Aberdeen, Scotland, United Kingdom; and Departments of †Oncology and ‡Pathology Aberdeen Royal Infirmary, Foresterhill Healthcare Campus, Foresterhill, Aberdeen, Scotland, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: Urquhart
authors.forename: Keith M
authors.initials: KM
authors.lastname: Kerr
authors.forename: Marianne
authors.initials: M
authors.lastname: Nicolson
authors.forename: Peh Sun
authors.initials: PS
authors.lastname: Loo
authors.forename: Ravi
authors.initials: R
authors.lastname: Sharma
authors.forename: Raj
authors.initials: R
authors.lastname: Shrimali
authors.forename: Russell D
authors.initials: RD
authors.lastname: Petty
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D015843:Serpins / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D015843:Serpins; C051072:squamous cell carcinoma-related antigen