title: A 13-gene signature prognostic of HPV-negative OSCC: discovery and external validation.
abstract: OBJECTIVE
  To identify a prognostic gene signature for patients with human papilloma virus (HPV)-negative oral squamous cell carcinomas (OSCC).
  
  
  METHODS
  Two gene expression datasets were used: a training dataset from the Fred Hutchinson Cancer Research Center (FHCRC, Seattle, WA; n = 97) and a validation dataset from the MD Anderson Cancer Center (MDACC, Houston, TX; n = 71). We applied L1/L2-penalized Cox regression models to the FHCRC data on the 131-gene signature previously identified to be prognostic in patients with OSCCs to identify a prognostic model specific for patients with high-risk HPV-negative OSCCs. The models were tested with the MDACC dataset using a receiver operating characteristic (ROC) analysis.
  
  
  RESULTS
  A 13-gene model was identified as the best predictor of HPV-negative OSCC-specific survival in the training dataset. The risk score for each patient in the validation dataset was calculated from this model and dichotomized at the median. The estimated 2-year mortality (± SE) of patients with high-risk scores was 47.1% (± 9.24%) compared with 6.35% (± 4.42) for patients with low-risk scores. ROC analyses showed that the areas under the curve for the age, gender, and treatment modality-adjusted models with risk score [0.78; 95% confidence interval (CI), 0.74-0.86] and risk score plus tumor stage (0.79; 95% CI, 0.75-0.87) were substantially higher than for the model with tumor stage (0.54; 95% CI, 0.48-0.62).
  
  
  CONCLUSIONS
  We identified and validated a 13-gene signature that is considerably better than tumor stage in predicting survival of patients with HPV-negative OSCCs. Further evaluation of this gene signature as a prognostic marker in other populations of patients with HPV-negative OSCC is warranted.
authors: Program in Epidemiology, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors: Pawadee
authors: P
authors: Lohavanichbutr
authors: Eduardo
authors: E
authors: Méndez
authors: F Christopher
authors: FC
authors: Holsinger
authors: Tessa C
authors: TC
authors: Rue
authors: Yuzheng
authors: Y
authors: Zhang
authors: John
authors: J
authors: Houck
authors: Melissa P
authors: MP
authors: Upton
authors: Neal
authors: N
authors: Futran
authors: Stephen M
authors: SM
authors: Schwartz
authors: Pei
authors: P
authors: Wang
authors: Chu
authors: C
authors: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality / Q000821:virology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality / Q000821:virology; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D027383:Papillomaviridae / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000401:mortality / Q000821:virology; D011379:Prognosis; D012372:ROC Curve; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor