School of Dentistry, Oral Pathology Department, Surgical Pathology Laboratory, University of Buenos Aires, Buenos Aires, Argentina.
Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBACONICET), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires y Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.
Cancer Biomark. 2021;32(1):37-48. doi: 10.3233/CBM-203086.
Stemness factors associated with tumorigenesis in different types of cancers have not been specifically studied in oral tongue SCC (OTSSC). Here, we aimed to quantify expression levels and distribution of KLF4 and SOX2, two relevant stemness factors, in oral SCC including OTSCC samples from different subsites.
We determined KLF4 and SOX2 expression levels by immunostaining 35 biopsies of OSCC. Stained wholeslide images were digitized and subjected to automatic cell detection and unbiased quantification using Qupath software. We found statistically significant reduction in KLF4 positive cells density (p= 0.024), and fraction (p= 0.022) in OTSCC from tongue borders compared with other tongue subsites. Instead, quantitative SOX2 analysis did not show differences in expression levels between OTSCC from the borders versus OTSCC developed in others subsites. Notably SOX2 expression was revealed increased in moderately and poorly differentiated OSCC compared with well differentiated ones (positive cells density p= 0.025, fraction p= 0.006). No significant correlation between KLF4 and SOX2 expression was observed, neither in OSCC nor in OTSCC.
KLF4 and SOX2 exhibit opposite expression profiles regarding subsite localization and differentiation level in OSCC. Our study prompts future OTSCC prospective studies looking for clinical prognosis to incorporate detailed subsite information in the analysis.
与不同类型癌症的肿瘤发生相关的干细胞因子尚未在口腔舌鳞状细胞癌（OTSCC）中专门研究。在这里，我们旨在定量表达水平和分布 KLF4 和 SOX2，两个相关的干细胞因子，在口腔 SCC 包括来自不同亚部位的 OTSCC 样本。
我们通过免疫染色 35 个 OSCC 活检来确定 KLF4 和 SOX2 的表达水平。染色的全玻片图像被数字化，并使用 Qupath 软件进行自动细胞检测和无偏量化。我们发现 KLF4 阳性细胞密度（p=0.024）和分数（p=0.022）在舌缘 OTSCC 中与其他舌亚部位相比统计学上显著降低。相反，定量 SOX2 分析显示 OTSCC 来自边界与其他亚部位发展的 OTSCC 之间的表达水平没有差异。值得注意的是，与分化良好的 OSCC 相比，中分化和低分化 OSCC 中 SOX2 的表达增加（阳性细胞密度 p=0.025，分数 p=0.006）。在 OSCC 中，KLF4 和 SOX2 之间没有观察到表达水平之间的显著相关性，在 OTSCC 中也没有观察到。
KLF4 和 SOX2 在 OSCC 中关于亚部位定位和分化水平表现出相反的表达谱。我们的研究提示未来 OTSCC 的前瞻性研究寻找临床预后，在分析中纳入详细的亚部位信息。
