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A genetic expression profile associated with oral cancer identifies a group of patients at high risk of poor survival
Journal article   Open access   Peer reviewed

A genetic expression profile associated with oral cancer identifies a group of patients at high risk of poor survival

Eduardo Méndez, John R Houck, David R Doody, Wenhong Fan, Pawadee Lohavanichbutr, Tessa C Rue, Bevan Yueh, Neal D Futran, Melissa P Upton, D Gregory Farwell, …
Clinical cancer research, Vol.15(4), pp.1353-1361
02/15/2009
DOI: 10.1158/1078-0432.CCR-08-1816
PMCID: PMC2683360
PMID: 19228736
url
https://doi.org/10.1158/1078-0432.CCR-08-1816View
Published (Version of record) Open Access

Abstract

To determine if gene expression signature of invasive oral squamous cell carcinoma (OSCC) can subclassify OSCC based on survival. We analyzed the expression of 131 genes in 119 OSCC, 35 normal, and 17 dysplastic mucosa to identify cluster-defined subgroups. Multivariate Cox regression was used to estimate the association between gene expression and survival. By stepwise Cox regression, the top predictive models of OSCC-specific survival were determined and compared by receiver operating characteristic analysis. The 3-year overall mean+/-SE survival for a cluster of 45 OSCC patients was 38.7+/-0.09% compared with 69.1+/-0.08% for the remaining patients. Multivariate analysis adjusted for age, sex, and stage showed that the 45 OSCC patient cluster had worse overall and OSCC-specific survival (hazard ratio, 3.31; 95% confidence interval, 1.66-6.58 and hazard ratio, 5.43; 95% confidence interval, 2.32-12.73, respectively). Stepwise Cox regression on the 131 probe sets revealed that a model with a term for LAMC2 (laminin gamma2) gene expression best identified patients with worst OSCC-specific survival. We fit a Cox model with a term for a principal component analysis-derived risk score marker and two other models that combined stage with either LAMC2 or PCA. The area under the curve for models combining stage with either LAMC2 or PCA was 0.80 or 0.82, respectively, compared with 0.70 for stage alone (P=0.013 and 0.008, respectively). Gene expression and stage combined predict survival of OSCC patients better than stage alone.
 Adult Aged Aged, 80 and over Carcinoma, Squamous Cell - genetics Carcinoma, Squamous Cell - mortality Carcinoma, Squamous Cell - pathology Female Gene Expression Profiling Humans Male Middle Aged Mouth Neoplasms - genetics Mouth Neoplasms - mortality Neoplasm Staging Principal Component Analysis Proportional Hazards Models Reverse Transcriptase Polymerase Chain Reaction

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