Investigation of expression levels of set-domain containing 2(SETD2) gene in anatomic sub-groups of head-neck cancers and evaluation of its relationship with clinicopathological parameters

Objective: Head and neck cancers (HNC) are a highly heterogeneous group of malignant diseases and consist of a complex group of cancers covering various anatomical regions and different etiologies. Environmental and genetic factors are involved in the development of the disease, but the underlying mechanisms are still unclear. There are no biomarkers for HNC that can be used routinely in clinical practice to predict the diagnosis, clinical response, recurrence or patient survival of the disease. The identification of new specific biomarkers for the early detection of HNC can greatly increase the survival rates and may also be helpful as a prognostic marker. SET Domain Containing 2 (SETD2) is the gene with histone lysine methyltransferase activity located in the p arm of chromosome 3, interacts with p53 and affects histone H3K36Me3. In the literature, there are studies examining the expression level of the SETD2 gene in many cancer types. However, there are no studies examining the differences in the expression status of the SETD2 gene in HNC subgroups. Within the scope of our study (İ.Ü.BAP-TTU-2022-38915), the expression of the SETD2 gene in tissue and body fluid samples of patients diagnosed with HNC and healthy volunteers was determined and the relationship between clinical parameters was investigated. In addition, it was aimed to determine the usability of the SETD2 gene as a biomarker in the early diagnosis and screening of head and neck cancers with invasive and/or non-invasive methods. Materials and Methods: The expression changes of the SETD2 gene were investigated by RNA isolation and cDNA synthesis from tumor, conjugate normal tissue, serum and saliva samples of 95 patients diagnosed with HNC and surgically treated, and normal mucosa, serum and saliva samples of 33 healthy individuals, respectively. Quantitative real-time polymerase chain reaction (QRT-PCR) method was used to determine the expression level. The results were compared with clinical parameters. Results: In the tumor tissue of the patients, compared to the conjugated normal tissue, the expression level was decreased in 47% and increased in 27%. While a 2.3-fold decrease in the expression level of the SETD2 gene was observed in tumor samples of patients with a diagnosis of HNC compared to the conjugated normal tissue, no significant fold change was detected in the increase in expression. Fold-change values of the patients were compared with clinical parameters, and statistical significance was found between the early stage and the decrease in expression levels (p<0.001). Statistical significance was found between the ΔCt values in the tumor tissue and its conjugate normal tissue (p=0.038), and between the ΔCt values in the tumor tissue and normal mucosa samples of the healthy individuals according to the Wilcoxon Rank 4 test (p=0.001). Correlations between the ΔCt values of the tissues and body fluids of the patients were examined, a moderate correlation was observed between tumor samples and conjugated normal tissue samples (p<0.001), and a weak correlation was observed between serum samples and saliva samples (p=0.003). Conclusions: It is thought that the SETD2 gene can be used as an invasive or non-invasive biomarker in the early diagnosis and screening of patients, provided that it is supported by studies involving larger patients in HNC patients. In addition, the expression profile of the SETD2 gene can be evaluated in predicting the stage of the disease in HNC. Keywords: head and neck cancer, expression, biomarker, SETD2