Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation

Abstract

Background: Trophoblast cell surface antigen 2 (TROP2) is overexpressed in many squamous cell carcinomas and promotes tumor development and invasion. The association between TROP2 expression and occurrence and development of oral squamous cell carcinoma (OSCC) remains to be understood. Methods: We investigated the role of TROP2 in OSCC patients using a combination of biophysical approaches. A total of 108 OSCC patient specimens with varying degrees of differentiation were subjected to hematoxylin and eosin staining, immunohistochemistry, Kaplan-Meier survival curve analysis, and atomic force microscopy to analyze TROP2 expression, morphology, and mechanical properties of OSCC tissues. Results: TROP2 was overexpressed in 34% of poorly differentiated OSCC samples. High levels of TROP2 were associated with 10.2% survival rate lower than 45.4% and patient age (odds ratio [OR] = 0.437, P = 0.039, 95% confidence interval [CI, 0.198-0.966]), tumor size (OR = 13.148, P = 0.000, 95% CI [5.060-34.168]), and TNM stage (OR = 0.141, P = 0.000, 95% CI [0.082-0.244]). Average surface roughness of low, medium, and highly differentiated OSCC tissues were 448.9 ± 54.8, 792.7 ± 83.6, and 993.0 ± 104.3 nm, respectively. The Pearson coefficient revealed a negative association between tumor stiffness and TROP2 expression (r = − 0.84, P < 0.01). Conclusion: Overexpression of TROP2 negatively associated with patient survival, degree of tumor differentiation, and tissue mechanics. Taken together, our findings demonstrated that TROP2 may be an indicator of OSCC differentiation leading to the altered mechanical properties of OSCC tissues.

Impact of Spatially Heterogeneous Trop-2 Expression on Prognosis in Oral Squamous Cell Carcinoma

“…To analyze the cytoplasmic expression, they used another primary antibody against Trop-2. Moreover, they did not compare central vs. peripheral expression [ 16 ]. Hence, their results are not directly comparable with ours.…”

“…In several cancer entities, Trop-2 protein expression may be used as an independent prognostic marker (summarized in [ 15 ]). In OSCC, high Trop-2 protein expression was reported to be associated with tumor grade and poor overall survival [ 16 , 17 ]. One reason may be the role of Trop-2 as an activator of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway in human OSCC cells [ 17 ].…”

The Role of TROP2 in BCC and Cutaneous SCC: A Clinical and Immunohistochemical Study

“…On the other hand, Zhang et al 25 reported a significant correlation of TROP2 with poorly differentiated oral SCC. Furthermore, TROP2 has been actively studied as a prognostic marker for various cancers including colon cancer and oral SCC.…”

“… 21 Although it is down-regulated in cholangiocarcinoma, 21 TROP2 was highly expressed in various human cancers as lung, 22 cervix 23 and oral SCC. 24 , 25 Regarding BCC and cutaneous SCC, the role of TROP2 was not yet identified.…”

Data on the effects of ECM rigidity on actomyosin contractility and invadopodia activity in individual versus pairs of head and neck squamous cell carcinoma cells

“…1 ) to hard ( Fig. 2 ) PAAs to mimic normal tissue and tumor-associated mechanical properties, respectively, in vitro [6] , [7] , [8] . Physical contact and interactions between HNSCC cells in pairs on the soft ( Fig.…”