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Comparative Study
. 2015 Feb 20;6(5):3443-51.
doi: 10.18632/oncotarget.2850.

Oncogenes and tumor suppressor genes in squamous cell carcinoma of the tongue in young patients

Affiliations
Comparative Study

Oncogenes and tumor suppressor genes in squamous cell carcinoma of the tongue in young patients

Andreas Knopf et al. Oncotarget. .

Abstract

Objectives: The occurrence of squamous cell carcinoma of the tongue (SCCT) of young patients increased. There are still controversies about patient prognosis. The underlying molecular mechanisms remain unclear.

Methods: 276 patients (66 ≤45, 210 >45 years) with SCCT were included. Clinical parameters and survival data were assessed. Oncogenes and tumor suppressors were analyzed via immunohistochemistry (p53, CXCR4, p16, EGFR) and qPCR (CDK4, CDKN2A, TP53, MDM2, AKT1, PIK3CA, NRAS, HRAS, KRAS, HGF, MET, EGF, ATM, BRCA1, E2F1, FHIT, RUNX3, STK11, BCL2, CTNNB1).

Results: The median overall survival was 142 (≤45 years) and 34 months (>45 years) (p < 0.0001; HR [95%CI]: 0.37 [0.30-0.58]). Disease specific survival in patients ≤45 years was with 181 months significantly higher than in patients >45 years (p < 0.0001; HR [95%CI]: 0.33 [0.26-0.57]). Immunhistochemistry visualized a comparable expression of analyzed proteins. QPCR demonstrated in patients ≤45 years a higher expression of genes that are associated with carcinogenesis (CTNNB1, STK11, CDKN2A, HGF, MET) as well as tumor suppressors that constitute an enhanced radio-sensitivity (ATM, BRCA1E2F1, FHIT).

Conclusion: Derogation of the WNT-CTNNB1-STK11 and CDKN2A-HGF-MET pathway can constitute the carcinogenesis, while the higher expression of radio-sensitizers ATM, BRCA1E2F1 and FHIT can explain the better OS/DSS in young patients.

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Conflict of interest statement

Conflict of interest

All authors sate no conflict of interest.

Figures

Figure 1
Figure 1. Kaplan-Meier estimates of the overall (OS) and disease specific survival in patients ≤45 years and patients >45 years
Figure 2
Figure 2. Immunohistochemistry (20x) of p53 (a, b), p16 (c, d), EGFR (e, f), and CXCR4 (g, h)
Tissue samples of the cohort of patients ≤45 years are visualized on the left, the cohort of patients >45 years on the.
Figure 3
Figure 3. Quantitative PCR of oncogenes and tumor suppressors
The relative expression is visualized for patients ≤45 years, normalized by patients >45 years. Significant differences were marked black.

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