Prognostic value of tumor lymphocytic infiltrate and PLK1 and FOXM1 expression in oral squamous cell carcinoma
Name: THABATA COELI DIAS DAMASCENO
Publication date: 25/07/2022
Advisor:
Name |
Role |
|---|---|
| SANDRA LÚCIA VENTORIN VON ZEIDLER | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| ADRIANA MADEIRA ALVARES DA SILVA | Internal Examiner * |
| GABRIELA TONINI PETERLE | Internal Examiner * |
| SANDRA LÚCIA VENTORIN VON ZEIDLER | Advisor * |
Summary: Oral squamous cell carcinoma (OSCC) has an estimated 377,713 new cases each year in the 2020-2022 triennium worldwide. Individuals affected by OSCC exhibit heterogeneous clinical behavior and diagnosis at an advanced stage, causing a worse prognosis. Early detection of the disease increases survival rates by up to 80%. Thus, the analysis of the dynamics between the immune response, through the analysis of the tumor lymphocytic infiltrate (TIL), and the tumor progression, evaluated by the use of the biomarkers PLK1 and FOXM1, can be essential tools to assist in the detection, recurrence and prognosis. of the disease. Serum PLK1 promoter region methylation, PLK1 and FOXM1 gene expression in tumor tissue, and Plk1 expression in tumor adjacent epithelium, dysplasia and tumor were evaluated as prognostic indicators in patients with OSCC. Plk1 expression was evaluated in 109 paraffinized tissue samples, 21 frozen tumor fragments and 30 serum (17 before treatment initiation and 13 after treatment). The Chi-Square and Fisher`s Exact tests
were used to establish an association between the variables studied with TIL density, methylation status and Plk1 expression; to compare the mean expression of Plk1 in the segments studied, the Mann-Whitney U test and the Bonferroni post-test were used; One-Way analysis of variance (ANOVA) and application of Dunnett and/or Tukey tests were applied to verify patterns of gene expression; and survival curves were evaluated using the Kaplan-Meier model. Low TIL density was associated with T3/T4 tumor size (p = 0.001) and clinical stage III/IV (p = 0.011); while high TIL was associated with T1/T2 tumor size (p = 0.001), clinical stage I/II (p = 0.01) and surgery as treatment performed (p = 0.046). The PLK1 methylation status showed no association with the variables analyzed. High expression of PLK1 was observed in 11
samples in relation to the control (p < 0.0001), as well as two samples had a different expression when in parity to the others (p < 0.0001). FOXM1 did not show expression in the sample group. The analysis of Plk1 expression in the segments showed a correlation between the adjacent epithelium pairs and the dysplasia and tumor regions (p < 0.001). High Plk1 expression was associated (p < 0.001) with the variables T3/4 tumor size, lymph node metastasis and stage III/IV. Likewise, low expression was associated (p < 0.001) with smaller tumor size, no lymph node involvement and early stages. Tumor Plk1 expression and TIL density were not shown to be prognostic factors when analyzed for the overall survival and disease-free survival curves, but they did show to be related to tumor development and progression in OSCC.
