MED15, transforming growth factor beta 1 (TGF-β1), FcγRIII (CD16), and HNK-1 (CD57) are prognostic biomarkers of oral squamous cell carcinoma

Abstract

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...

Assessing the effect of human dental pulp mesenchymal stem cell secretome on human oral, breast, and melanoma cancer cell lines

“…The significantly attenuated anti-inflammatory cytokine implicated in the progression of AW-13516 is TGF-β1. Increased TGF-β1 is associated with increased overall survival in oral cancer ( Elahi and Rakhshan, 2020 ), thus a reduced TGF- β1 as seen in the present study could have augmented one or more of the carcinogenic properties.…”

Clinical and Histopathological Factors Associated with the Tumoral Expression of TGF-β1, MED15, CD16, and CD57 in Oral Squamous Cell Carcinoma

“…Some prognostic biomarkers are not assessed adequately (or at all) in terms of their associated factors. These include MED15, transforming growth factor beta 1 (TGF- β 1), CD16, and CD57 [ 2 , 3 ].…”

“…TGF- β 1 is a cytokine with contradictory properties [ 4 – 6 ]. It can both suppress and induce tumorigenesis depending on the situation even in one tumor type [ 3 – 6 ]. Studies on factors associated with its tumoral overexpression are a few and controversial [ 6 ].…”

“…CD16 is an IgG Fc receptor on the surface of inflammatory cells [ 3 , 7 ]. It plays a key role in antibody-dependent cellular cytotoxicity which is responsible for defense against tumor cells [ 3 , 7 ].…”

“…CD16 is an IgG Fc receptor on the surface of inflammatory cells [ 3 , 7 ]. It plays a key role in antibody-dependent cellular cytotoxicity which is responsible for defense against tumor cells [ 3 , 7 ]. In this regard, any factors associated with tumoral expression of CD16 have not been assessed in SCC or any other cancers.…”