Identification and validation of gene expression models that predict clinical outcome in patients with early-stage laryngeal cancer.
BACKGROUND
Despite improvement in therapeutic techniques, patients with early-stage laryngeal cancer still recur after treatment. Gene expression prognostic models could suggest which of these patients would be more appropriate for testing adjuvant strategies.


METHODS
Expression profiling using whole-genome DASL arrays was carried out on 56 formalin-fixed paraffin-embedded tumor samples of patients with early-stage laryngeal cancer. We split the samples into a training and a validation set. Using the supervised principal components survival analysis in the first cohort, we identified gene expression profiles that predict the risk of recurrence. These profiles were then validated in an independent cohort.


RESULTS
Gene models comprising different number of genes identified a subgroup of patients who were at high risk of recurrence. Of these, the best prognostic model distinguished between a high- and a low-risk group (log-rank P<0.005). The prognostic value of this model was reproduced in the validation cohort (median disease-free survival: 38 versus 161 months, log-rank P=0.018), hazard ratio=5.19 (95% confidence interval 1.14-23.57, P<0.05).


CONCLUSIONS
We have identified gene expression prognostic models that can refine the estimation of a patient's risk of recurrence. These findings, if further validated, should aid in patient stratification for testing adjuvant treatment strategies.
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
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E
Fountzilas
Department of Otorhinolaryngology, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki.
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K
Markou
Department of Otorhinolaryngology, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki.
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K
Vlachtsis
Department of Otorhinolaryngology, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki.
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A
Nikolaou
Department of Pathology.
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Arapantoni-Dadioti
Department of Pathology.
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E
Ntoula
Department of Otorhinolaryngology, "Metaxa" Cancer Hospital, Piraeus.
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G
Tassopoulos
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Thessaloniki.
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M
Bobos
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.
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P
Konstantinopoulos
Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
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G
Fountzilas
Division of Hematology/Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA. Electronic address: dspentzo@bidmc.harvard.edu.
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D
Spentzos
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005557:Formaldehyde; D020022:Genetic Predisposition to Disease; D006801:Humans; D007822:Laryngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D011379:Prognosis; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D016707:Tissue Fixation
D005557:Formaldehyde