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Clinical and genetic signatures of local recurrence in oral squamous cell carcinoma.
Archives of Oral Biology 2018 August 7
PURPOSE: Recurrent and metastatic Oral Squamous Cell Carcinoma (OSCC) is often incurable. There are large gaps in the understanding of the clinical course, biology and genetic biomarkers of OSCC which could help us identify patients with high-risk of recurrence who may benefit from intensified therapy or novel targeted therapy trials. The purpose of this study was to identify significant clinical, pathological and genomic risk factors for local recurrence in OSCC.
PATIENTS AND METHODS: Molecular data sets and clinicopathological characteristics of 159 head and neck carcinoma patients were obtained from The Cancer Genome Atlas (TCGA) data portal and analyzed using the Genome Data Analysis Center and cBioPortal to find significant risk factors for tumor recurrence.
RESULTS: The local recurrence rate was 24%. OSCC originating from the buccal mucosa composed 13% of all the tumors in the recurrent group, making it a statistically significant risk of recurrence (P value = 0.03). Likewise, positive surgical margins, pathological T staging, and alcohol consumption were found to be significantly associated with recurrence (P value < 0.05). Genetic profiling revealed the top 5 mutated genes (using the MutSigCV analysis). Only one of these genes, CASP8 was the only gene that was significantly altered only in the recurrent group (Q value = 8.7 × 10-11 ). The fingerprint of 5 mutated genes was found in 97% of the patients in the recurrence group. Moreover, copy number alterations in cytoband 5p15.33, which involved amplification in telomerase reverse-transcriptase (TERT) gene, was found to be significant only in the recurrent group.
CONCLUSIONS: In the current study, we found several clinical and genetic characteristics that could define patients with high-risk of OSCC recurrence. This provides a means of identifying patients that may benefit from intensified therapy or novel targeted therapy trials.
PATIENTS AND METHODS: Molecular data sets and clinicopathological characteristics of 159 head and neck carcinoma patients were obtained from The Cancer Genome Atlas (TCGA) data portal and analyzed using the Genome Data Analysis Center and cBioPortal to find significant risk factors for tumor recurrence.
RESULTS: The local recurrence rate was 24%. OSCC originating from the buccal mucosa composed 13% of all the tumors in the recurrent group, making it a statistically significant risk of recurrence (P value = 0.03). Likewise, positive surgical margins, pathological T staging, and alcohol consumption were found to be significantly associated with recurrence (P value < 0.05). Genetic profiling revealed the top 5 mutated genes (using the MutSigCV analysis). Only one of these genes, CASP8 was the only gene that was significantly altered only in the recurrent group (Q value = 8.7 × 10-11 ). The fingerprint of 5 mutated genes was found in 97% of the patients in the recurrence group. Moreover, copy number alterations in cytoband 5p15.33, which involved amplification in telomerase reverse-transcriptase (TERT) gene, was found to be significant only in the recurrent group.
CONCLUSIONS: In the current study, we found several clinical and genetic characteristics that could define patients with high-risk of OSCC recurrence. This provides a means of identifying patients that may benefit from intensified therapy or novel targeted therapy trials.
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