Focal adhesion kinase is overexpressed in thymic epithelial tumors and may serve as an independent prognostic biomarker

Abstract

Focal adhesion kinase (FAK) has long been considered to be a key regulator of growth factor receptor- and integrin-mediated signals, with pivotal roles in tumor cells through its kinase activity and scaffolding function. Increased FAK expression and activity has been observed in tumors of various origins and is often associated with a poor prognosis. However, there have been no studies on the aberrant expression of FAK in thymic epithelial tumors to date. The aim of the present study was to evaluate FAK expression in thymic epithelial tumors and to explore the prognostic significance of FAK. FAK expression was investigated in 100 formalin-fixed, paraffin-embedded human thymic epithelial tumor (TET) specimens using immunohistochemical analysis with FAK-specific monoclonal antibody 4.47, and the associations between FAK expression and clinicopathological parameters (including sex, age, tumor size, myasthenia gravis, World Health Organization classification and Masaoka-Koga stage) were analyzed. FAK was significantly overexpressed in TETs compared with in normal thymus tissues (P<0.001). Additionally, FAK overexpression was significantly associated with advanced tumor stages (stages III or IV; P<0.001) and highly aggressive TET subtypes (type B2 and B3 thymomas and thymic carcinomas; P<0.001). Furthermore, FAK overexpression was significantly associated with a worse 10-year overall survival, as determined by univariate analysis (P<0.001). Multivariate analysis revealed that FAK overexpression was an independent prognostic factor for patients with TETs (P=0.034). The results of the present study suggest that FAK serves an important role in the tumorigenesis and progression of TETs. Therefore, FAK may serve as a prognostic biomarker and is a potential therapeutic target for the treatment of TETs.

Discovery and validation of DNA methylation markers for overall survival prognosis in patients with thymic epithelial tumors

“…However, the drawback is that there is no comparison with the current Masaoka staging system. Literature had also reported that overexpression of focal adhesion kinase ( FAK ) protein in TETs was associated with poor prognosis and may serve as an independent prognostic biomarker for TETs [30]. Xu RH et al reported that DNA methylation sites can be used for tumor diagnosis and prognosis, which further support our current findings [31].…”

Identification of Molecular Characteristics and New Prognostic Targets for Thymoma by Multiomics Analysis

“…There were 34% of the genes in the ECM-receptor interaction pathway mutated repeatedly in cancer [ 31 ]. Focal adhesion kinase (FAK) is highly expressed in thymic epithelial tumors and can be used as an independent prognostic biomarker [ 32 ]. PPAR γ overexpression more than doubled insulin-stimulated thymoma viral protooncogene phosphorylation during low lipid availability [ 33 ].…”

Molecular and Functional Key Features and Oncogenic Drivers in Thymic Carcinomas

“…The relevance of the interaction between the thymic stroma and extracellular matrix is underscored by the overexpression of focal adhesion kinase (FAK) in thymic epithelial tumors, especially in highly aggressive subtypes like type B2 and B3 thymomas and thymic carcinomas [ 56 ].…”