Unlike TGF-β1, MMP-9 might be useful for prognosis determination.

Owing to the high incidence and mortality of oral squamous cell carcinoma (OSCC), knowledge of its diagnostic and prognostic factors is of significant value. The biomarkers 'CD16, CD57, transforming growth factor beta 1 (TGF-β1), and MED15' can play crucial roles in tumorigenesis, and hence might contribute to diagnosis, prognosis, and treatment. Since there was no previous study on MED15 in almost all cancers, and since the studies on diagnostic/prognostic values of the other three biomarkers were a few in OSCC (if any) and highly controversial, this study was conducted. Biomarker expressions in all OSCC tissues and their adjacent normal tissues available at the National Tumor Bank (n = 4 biomarkers × [48 cancers + 48 controls]) were estimated thrice using qRT-PCR. Diagnostic values of tumors were assessed using receiver-operator characteristic (ROC) curves. Factors contributing to patients' survival over 10 years were assessed using multiple Cox regressions. ROC curves were used to estimate cutoff points for significant prognostic variables (α = 0.05). Areas under the curve pertaining to diagnostic values of all markers were non-significant (P > 0.15). Survival was associated positively with tumoral upregulation of TGF-β1 and downregulation of CD16, CD57, and MED15. It was also associated positively with younger ages, lower histological grades, milder Jacobson clinical TNM stages (and lower pathological Ns), smaller and thinner tumors, and surgery cases not treated with incisional biopsy (Cox regression, P < 0.05). The cutoff point for clinical stage-as the only variable with a significant area under the curve-was between the stages 2 and 3. Increased TGF-β1 and reduced CD16, CD57, and MED15 expressions in the tumor might independently favor the prognosis. Clinical TNM staging might be one of the most reliable prognostic factors, and stages above 2 can predict a considerably poorer prognosis. Oral squamous cell carcinoma (OSCC) is a common oral cancer (90% of oral cancers) and has a poor prognosis 1-4. It is aggressive and can modulate the immune system through evasion and direct/indirect suppression 3,5-7. High rates of recurrence despite numerous treatments imply that current treatments and prognostic predictors are not efficient 3,7,8. These call for investigating new diagnostic, prognostic, and possibly therapeutic markers for SCC. Many factors might play a role in cancer prognostication, including tobacco, alcohol, human papilloma virus, demographic/clinical/histopathological factors (such as stage, grade, or tumor budding), and biomarkers (such as Gas6) 9-11. SCCs of head and neck might be immune-modulatory, and the prognostic effects of immune system activity have been conflicting 3,5,12-17. The interaction between tumor cells and the immune system is crucial in tumorigenesis and improved knowledge of dysregulated pathways might allow identification of new targets 18,19. Therefore, the assessment of diagnostic and prognostic roles of biomarkers such as transforming growth factor beta 1 (TGF-β1), CD16, CD...

Introduction. Factors associated with the expression of oral squamous cell carcinoma (OSCC) biomarkers “CD16, CD57, TGF-β1, and MED15” are not assessed, except in few controversial studies of some of these biomarkers. This study aimed to highlight factors that can correlate with tumoral overexpression of these biomarkers. Methods. In this genetically-matched case-control study, biomarker expressions in all available OSCC tissues and their adjacent normal tissues at the National Tumor Center (n = 384 (4 biomarkers × (48 cancers + 48 controls))) were measured using qRT-PCR. Factors associated with tumoral overexpression of CD16, CD57, TGF-β1, and MED15 (compared to the benign control) were evaluated, using log-level multiple linear regressions and Spearman (α = 0.05). Results. Tumoral CD16 upregulation was observed in younger patients (β = −0.284, P = 0.040 ) and cigarette smokers (β = 0.397, P = 0.005 ). Tumoral CD57 was upregulated in males (β = 0.341, P = 0.008 ), smokers (β = 0.401, P = 0.002 ), and cases without vascular invasion (β = −0.242, P = 0.042 ). Tumoral TGF-β1 was elevated in smokers (β = 0.452, P = 0.001 ) and smaller tumors (β = −0.322, P = 0.045 ). Tumoral MED15 was overexpressed in smokers (β = 0.295, P = 0.036 ) and cases lacking perineural invasion (β = −0.394, P = 0.007 ). Conclusion. As the most consistent finding, smoking might be positively associated with tumoral overexpression of all biomarkers. Tumoral increase in CD57 might be positively associated with metastasis while being negatively correlated with vascular and lymphatic invasion. Tumor size might be negatively associated with tumoral TGF-β1 expression.

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