Cancer Biology

Oral Squamous Cell Carcinoma (OSCC) is a major cause of cancer death worldwide, which is mainly due to recurrence leading to treatment failure and patient death. Histological status of surgical margins is a currently available assessment for recurrence risk in OSCC; however

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histological status does not predict recurrence, even in patients with histologically negative margins. Therefore, molecular analysis of histologically normal resection margins and the corresponding OSCC was studied for a gene signature predictive of recurrence.

Ameta-analysis of 199 samples (OSCCs and normal oral tissues) from five public microarray datasets was used, in addition to microarray analysis of 96 OSCCs and histologically normal margins from 24 patients, to train a gene signature for recurrence. Validation was performed by quantitative real-time PCR using 136 samples from an independent cohort of 30 patients.

Altogether 138 significantly over-expressed genes (>2-fold, false discovery rate of 0.01) were identified in OSCC. By penalized likelihood Cox regression, a 4-gene signature with prognostic value for recurrence in the training set was identified. This signature comprised the invasion-related genes MMP1, COL4A1, P4HA2, and THBS2. Over-expression of this 4-gene signature in histologically normal margins was associated with recurrence in the training cohort (p=0.0003, logrank test) and in independent validation cohort (p=0.04, HR=6.8, logrank test).

Gene expression alterations occur in histologically normal margins in OSCC. Over-expression of the 4-gene signature in histologically normal surgical margins was validated and highly predictive of recurrence in an independent patient cohort. These findings may be applied to develop a molecular test, which would be clinically useful to help predict which patients are at a higher risk of local recurrence.

Authors: Patricia P Reis , Levi Waldron , Bayardo Perez-Ordonez , Melania Pintilie , Natalie Naranjo Galloni, Yali Xuan , Nilva K Cervigne , Giles C Warner , Antti A Makitie, Colleen Simpson, David Goldstein, Dale Brown, Ralph Gilbert, Patrick Gullane, Jonathan Irish, Igor Jurisica and Suzanne Kamel-Reid.

Link: http://www.biomedcentral.com/content/pdf/1471-2407-11-437.pdf