TROP2 belongs to the calcium signal transduction gene family associated with tumors and found in human trophoblast and chorionic cell lines. Studies have shown that overexpression of TROP2 is associated with tumorigenesis and malignancy [28–30]. In this study, TROP2 expression was observed to be a highly sensitive and specific marker of tongue squamous cell carcinoma and tissue stiffness; relative thickness of samples helps accurately accurate diagnose and determine the staging of tongue squamous cell carcinoma.
Immunohistochemical analysis revealed that the expression of TROP2 in poorly differentiated OSCC tissues was significantly higher than that in well-differentiated OSCC tissues. Additionally, TROP2 upregulation closely correlated with tumors of advanced TNM (III + IV) staging and poor differentiation than that of tumors with low TNM (I + II) staging. Thus, the abnormal expression of TROP2 correlates with the occurrence and development of tongue malignancies. Furthermore, high TROP2 expression predicts low survival as compared to that of the tumors with low TROP2 expression. Previous research has also demonstrated shorter patient lifespan with high levels of TROP2 as compared to patients with laryngeal squamous cell carcinoma and low levels of TROP2 [31]. TROP2 possesses sites for tyrosine/serine phosphorylation that regulate signal transduction or regulatory factor, thereby imparting resistance to apoptosis in cancer cells [32]. Upregulated TROP2 correlates with the poor prognosis of thyroid papillary carcinoma [33], colon cancer [34], liver cancer [35], and other malignant tumors.
There have been an increasing number of studies on the biological role of TROP2 at the molecular level. TROP2 promotes PTEN which is type of tumor suppressor gene and negatively regulates PI3K/AKT signaling, thereby stimulating tumor development [14]. PTEN is a well-known tumor suppressor that is a phosphatase [36] and affects the PI3K/PKB/AKT channel during the dephosphorylation of PIP-2 and PIP-3 [37]. PI3K signaling is important in regulating tumor cell proliferation, migration, and invasion [38, 39]. Thus, PTEN is a negative regulator of cancer [40, 41]. Li et al. have shown that TROP2 activates epithelial–mesenchymal transition via PI3K/AKT signaling, thereby promoting proliferation, migration, and metastasis in gallbladder cancer cells [42]. Similarly, TROP2 expression stimulates the proliferation, migration, and invasion of osteosarcoma cells [43]. Hou et al. demonstrated that TROP2 also regulates JAK2/STAT3 signaling in glioblastoma cells [44].
Functional differentiation of tissues influenced the micro-morphology and mechanical stiffness of OSCC cells. We detected low surface roughness of OSCC tissues with a loose structure, reduced hardness, and enhanced adhesion, cell migration, and invasion. Poorly differentiated OSCC tissues are "softer" than highly differentiated OSCC tissues. PI3K is an important cell adhesion molecule. TROP2 triggers the synthesis of proteins with homologous domains, such as pleckstrin, RAC, Tiam, and Vav. Tiam and Vav activate RAC that leads to the reorganization of the actin cytoskeleton, cell recognition, and adhesion [45].
The underlying mechanisms involved in the changes in the micromechanical properties of OSCC samples and occurrence, development, metastasis, and invasion of OSCC tumors was yet to be elucidated. HE staining is a gold standards for tumor diagnosis. With the development of biomechanics in the last two decades [46, 47], the testing of tissue mechanical properties needs revisiting based on the biomedical physical parameters. In this study, we have considered the changes in the mechanical properties at the micro-nanometer level by AFM and determined the correlation between the TNM grade, metastasis, and stiffness of tumor samples. Thus, one limitation in the present study is lack of molecular methods for confirmatory identification, such as WB or Elisa. And the small sample size were limitations in our study.