Abstract
Transforming acidic coiled-coil-containing protein 3 (TACC3), a microtubule regulator, is associated with various cancers. However, the relationship between TACC3 and soft tissue sarcomas (STS) remains unclear. We investigated the expression of TACC3 in 136 STS patient samples using immunohistochemical (IHC) staining, and the statistical associations between TACC3 expression and clinicopathological characteristics were evaluated. Additionally, the expression levels of the tumor suppressor p53 and of the cell proliferation marker Ki-67 were also assessed by IHC. High TACC3 expression was detected in 94/136 of STS cases (69.1%), and significantly correlated with higher grade according to the French Fédération Nationale des Centres de Lutte Contre le Cancer system (P<0.0001), poorer tumor differentiation (P<0.0001), increased mitotic counts (P<0.0001), advanced stage per American Joint Committee on Cancer guidelines (P<0.0001), higher p53 expression (P = 0.0487), higher Ki-67 expression (P<0.0001), and undergoing postoperative therapy (P = 0.0001). Disease-free survival (DFS) and overall survival (OS) of patients with high TACC3 expression were significantly shorter (P<0.0001 and P<0.0001, respectively). On multivariate analyses, high TACC3 expression was an independent negative prognostic factor for both DFS and OS (hazard ratio [HR]: 3.074; P = 0.0235 and HR: 8.521; P = 0.0415, respectively). Our results suggest that TACC3 is an independent prognostic factor and may be a novel therapeutic target for the treatment of STS.
Highlights
Soft tissue sarcomas (STS) are rare, and comprise a heterogeneous group of mesenchymal tumors
Our study revealed that Transforming acidic coiled-coil-containing protein 3 (TACC3) was highly expressed in more than two-thirds of STS patients, and that greater expression was associated with higher FNCLCC grade, poorer tumor differentiation, increased mitotic counts, advanced American Joint Committee on Cancer (AJCC) stage, higher p53 expression, higher Ki-67 expression, and undergoing postoperative therapy
Higher TACC3 expression was associated with poorer tumor differentiation of FNCLCC in STS
Summary
Soft tissue sarcomas (STS) are rare, and comprise a heterogeneous group of mesenchymal tumors. They account for less than 1% of all human malignancies [1], they exhibit very aggressive behavior; approximately half of the patients with STS experience tumor. TACC3, an Aurora A kinase target, is essential for microtubule growth and stability when localizing to the centrosome during mitosis [6]. Abnormality of microtubules/centrosomes causes mitotic spindle defects and correlates with tumorigenesis and tumor progression; the involvement of TACC3 in various cancers has been reported [7]. Despite the recent development of chemotherapeutic drugs that target mitotic proteins such as Aurora kinase and Polo-like kinase, their effects remain ambiguous [9]. TACC3 itself is being examined as a potentially novel therapeutic target
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