Investigation of miRNAs and protein biomarkers associated with PI3K and wnt signaling pathways in oral squamous cell carcinoma and risk groups

Oral squamous cell carcinoma (OSCC) is a malign neoplasm originating from mouth squamous epithelium cells, it has poor prognosis as it is usually diagnosed in advanced stages, 5-year survival rate is 35-50%. Fanconi anemia (FA) is a rare bone marrow deficiency syndrome due to the DNA repair gene mutations, and OSCC is seen at younger ages and more frequently in FA patients than in the general population. Tobacco smokers also have risk of developing OSCC. It is important to determine biomarkers which could be used for OSCC diagnosis, treatment, or prognosis evaluation in these groups. PI3K and Wnt are effective signaling pathways in the molecular pathogenesis of OSCC. The aim of this research is investigation of biomarkers that can be used for OSCC by measuring salivary expression levels of miR-9, miR 34a and miR-196a and serum protein levels of survivin, CIP2A and β-catenin, which are associated with PI3K and Wnt signaling pathways in OSCC patients, FA patients and smokers. miRNA levels were determined with Quantitative PCR. The expression levels of miRNA were normalized and compared between OSCC patients, FA patients, and smoking and non-smoking healthy control groups. Protein levels were determined with ELISA. This is the first study, in which miRNA and proteins which may be related to PI3K and Wnt signaling pathways are being examined among OSCC patients, FA patients and smokers. According to our data, miR-9 and miR-34a levels in OSCC patients were lower compared to control groups (p=0,01 and p=0,012), and there was no significant difference in miR-196a levels (p>0,05). In OSCC patients, miR-9 level was related to lymph node metastasis (p=0,04). The difference in miRNA levels among smokers and non-smokers were not determined (p>0,05). In FA patients, miR-9 and miR-34 levels were lower than in control groups, likewise the OSCC patients (p=0,017 and p=0,014). In OSCC patients, survivin and CIP2A protein levels were determined as higher (p=0,04, p= p<0,001), but ß-catenin levels as lower (p=0,034). A negative correlation was observed between the levels of survivin and miRNA-34a (p=0,005). In FA patients, survivin levels were higher than OSCC patients and healthy control groups (p=0,01), but ß-catenin levels were lower (p=0,008). miR-9 and CIP2A are important as biomarkers in OSCC. Usage of tobacco was observed to effect survivin levels. In FA patients, close follow up of the levels of miR-9, miR-34, survivin, and ß-catenin would be appropriate considering OSCC development. We are of the opinion that, increasing the number of patients and multicentric systematic studies would support our results.