Prognostic Value of Focal Adhesion Kinase (FAK) in Human Solid Carcinomas: A Meta-Analysis

Abstract

BackgroundRecently, the number of reports on focal adhesion kinase (FAK) as a vital therapeutic target in solid carcinomas has increased; however, the prognostic role of FAK status remains poorly understood. This study aims to evaluate the prognostic effect of FAK by means of a meta-analysis.MethodsWe performed a systematic literature search in order to examine the correlation between expression of FAK and overall survival(OS). The hazard ratio (HR) of OS was used to measure survival. A random-effects model was used to pool study statistics. Sensitivity and publication bias analyses were also conducted.ResultsThirty eligible studies involving 4702 patients were included. The median expression rate of FAK was 54%. Meta-analysis of the HRs demonstrated that high FAK expression was associated with worse OS (average HR = 2.073, 95%confidence interval[CI]:1.712–2.510, p = 0.000). Regarding cancer type, FAK was associated with worse OS in gastric cancer (HR = 2.646,95% CI:1.743–4.017, p = 0.000), hepatocellular carcinoma (HR = 1.788,95% CI:1.228–2.602, p = 0.002), ovarian cancer (HR = 1.815, 95% CI: 1.193–2.762, p = 0.005), endometrial cancer (HR = 4.149, 95% CI:2.832–6.079, p = 0.000), gliomas (HR = 2.650, 95% CI: 1.205–5.829, p = 0.015), and squamous cell carcinoma (HR = 1,696, 95% CI: 1.030–2.793, p = 0.038). No association was found between HR and disease staging according to our meta-regression analysis.ConclusionsOur study shows that high expression of FAK is associated with a worse OS in patients with carcinomas, but the association between FAK and prognosis varies according to cancer type. The value of FAK status in clinical prognosis in cancer needs further research.

Focal adhesion kinases in head and neck squamous cell carcinoma

“…FAK activity and expression in tumors have been linked to cancer initiation, progression, metastasis, and poor prognosis. In the present study, FAK expression was higher in tumors than in AE, and these findings were consistent with previous researches . The same result was observed with phosphorylated forms of FAK, suggesting the involvement of these 3 adhesion molecules in the development of HNSCC.…”

The clinical and biological implications of the focal adhesion kinase pathway in ShenLingLan mediated suppression of cellular migration of ovarian cancer cells

“…Results from our clinical cohort suggest that ovarian cancer is similar to other solid tumours, including breast and lung, in which increased transcript copy numbers of FAK and paxillin are linked to poor prognosis [23][24][25][26][27][28]. Our clinical cohort isolated those groups of patients who had poorly differentiated tumours, and those patients who died from the disease and/or had associated incidence.…”

The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation

“…A central mediator of adhesion-dependent signaling, the role of FAK in mechanotransduction is regarded as being less in the generation of cellular tension and more in the transduction of signals downstream of mechanical cell-matrix interactions [65][66][67] . Nonetheless, its demonstrated importance in both functional mechanical signaling [68][69][70][71] and in the biology of EOC [72][73][74][75][76][77] prompted us to assess the effect of FAK inhibition on the EOC mechano-response. Unlike blebbistatin and fasudil, treatment of SKOV3 cells with PF-271 (also known as PF-562271), a potent and highly selective inhibitor of FAK, had no significant effect on cellular traction force ( Figure 8C and D) or stress fiber and phospho-MLC architecture ( Figure 8G and I), but significantly reduced phospho-FAK intensity while preserving or slightly enhancing focal adhesion size and aspect ratio ( Figure 8E and F), consistent with FAK's role in focal adhesion turnover 78 .…”