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

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RESEARCH ARTICLE

Open Access

Tissue mechanics and expression of TROP2 in oral squamous cell carcinoma with varying differentiation Baoping Zhang1,2†, Shuting Gao1†, Ruiping Li1†, Yiting Li1, Rui Cao1, Jingyang Cheng1, Yumeng Guo1, Errui Wang1, Ying Huang1 and Kailiang Zhang1*

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. Keywords: Oral squamous cell carcinoma, TROP2, Tissue stiffness, Differentiation, Survival

Background Oral squamous cell carcinoma (OSCC) is a common subtype of head and neck and other malignant tumors [1, 2]. The past few decades have shown increased incidence of OSCC that is expected to rise further in the future [3]. Therefore, it is imperative to determine * Correspondence: [email protected] † Baoping Zhang, Shuting Gao and Ruiping Li contributed equally to this work. 1 Department (Hospital) of Stomatology, Lanzhou University, Donggang west Road 199, Lanzhou 730000, Gansu, China Full list of author information is available at the end of the article

biological factors associated with the early diagnosis and treatment of OSCC. Human trophoblast cell surface antigen 2 (TROP2), also called tumor-associated calcium signal transduction-2 (TACSTD-2), is a surface glycoprotein encoded by TACS TD that has extracellular domains, a single transmembrane domain, and a short tail [4, 5]. TROP2 is overexpressed in many human cancers, including ovarian [6, 7], gastric [8, 9], colorectal [10], pancreatic [11], and laryngeal cancers [