Overexpression of caldesmon is associated with lymph node metastasis and poorer prognosis in patients with oral cavity squamous cell carcinoma

Abstract

BACKGROUND A previous comparative tissue proteomics study by the authors of the current study led to the identification of caldesmon (CaD) as one of the proteins associated with cervical metastasis of oral cavity squamous cell carcinoma (OSCC). In the current investigation, the authors focused on the potential functions of CaD in patients with OSCC. METHODS CaD expression was examined in tissue samples from 155 patients using immunohistochemical analysis. The expression of CaD variants was determined by Western blot analysis and reverse transcriptase‐polymerase chain reaction. In addition, the specific effects of CaD gene overexpression and silence were determined in OSCC cell lines. RESULTS CaD expression was found to be significantly higher in tumor cells from metastatic lymph nodes compared with primary tumor cells, and was nearly absent in normal oral epithelia. Higher CaD expression was found to be correlated with positive N classification, poor differentiation, perineural invasion, and tumor depth (P = .001, P = .029, P = .001, and P = .031, respectively). In survival analyses, OSCC patients with higher CaD expression were found to have poorer prognosis with regard to disease‐specific survival and disease‐free survival (P = .003 and P = .014, respectively). Multivariate analyses further indicated that higher CaD expression was an independent predictor of disease‐specific survival (P = .043). Serum CaD levels were found to be significantly higher in patients with OSCC, but this finding was not associated with clinicopathological manifestations. Data obtained from in vitro suppression, rescue, and overexpression of CaD in OEC‐M1 cells indicated that CaD promotes migration and invasive processes in OSCC cells. CONCLUSIONS The findings of the current study collectively suggest that the low‐molecular‐weight CaD expression in OSCC tumors is associated with tumor metastasis and patient survival. Cancer 2013;119:4003–4011. © 2013 American Cancer Society.

Low-molecular-mass secretome profiling identifies HMGA2 and MIF as prognostic biomarkers for oral cavity squamous cell carcinoma

“…Images of stained slides were obtained using a ScanScope CT automated slide-scanning system (Aperio Technologies, Vista, CA). The expression level of HMGA2 or MIF was scored using a combined scoring method that accounted for both the staining intensity and the percentage of stained cells, as previously described 14 20 52 53 54 . Strong, moderate, weak, and negative staining intensities were scored as 3, 2, 1, and 0, respectively.…”

Overexpression of caldesmon is associated with tumor progression in patients with primary non-muscle-invasive bladder cancer

“…CAD is a major actomyosin binding protein that is critically implicated in the regulation of the microfilament network, and acts as an important modulator of various cell functions. CAD expression and its role in several solid cancers have been reported in recent studies [ 11 – 15 ]. However, the results are conflicting.…”

Revelation of fibroblast protein commonalities and differences and their possible roles in wound healing and tumourigenesis using co‐culture models of cells

“…CALD1 participates in the interaction of actin and myosin and its expression and function in MFs has been studied (Lazard et al., ; Kalekou et al., ; Hai and Gu, ; Council and Hameed, ; Huang et al., ; Leung et al., ; Salgueiredo‐Giudice et al., ). Elevated expression of this protein was also observed in oral SCCs (Méndez et al., ) and its overexpression was associated with lymph node metastasis and poor prognosis in patients with oral cavity SCC (Chang et al., ). Additionally, it was shown that CALD1 phosphorylation reduced its binding to actin and myosin thus promoting pro‐migratory and pro‐invasive activities in breast cancer cells (Schwappacher et al., ).…”