Overexpression of Caldesmon Is Associated With Lymph Node Metastasis and Poorer Prognosis in Patients With Oral Cavity Squamous Cell Carcinoma
Overexpression of Caldesmon Is Associated With Lymph Node Metastasis and Poorer Prognosis in Patients With Oral Cavity Squamous Cell Carcinoma
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DOI：
10.1002/cncr.28300
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发表时间：
2013-11-15
期刊：
影响因子：
6.2
通讯作者：
Chi, Lang-Ming
中科院分区：
文献类型：
--
作者：
Chang, Kai-Ping;Wang, Chih-Lueh Albert;Chi, Lang-Ming
本研究的作者先前的比较组织蛋白质组学研究鉴定了钙调蛋白（CaD）作为与口腔鳞状细胞癌（OSCC）颈部转移相关的蛋白质之一。在目前的调查中，作者专注于CaD在OSCC患者中的潜在功能。METHODSCaD的表达进行了检查，从155例患者的组织标本，采用免疫组化分析。通过Western印迹分析和逆转录聚合酶链反应测定CaD变体的表达。此外，在OSCC细胞系中测定了CaD基因过表达和沉默的特异性效应，发现在转移淋巴结的肿瘤细胞中，CaD基因的表达显著高于原发肿瘤细胞，而在正常口腔上皮中几乎不表达。较高的CaD表达与阳性N分类、低分化、神经周围浸润和肿瘤深度相关（分别为P= 0.001、P= 0.029、P= 0.001和P= 0.031）。在生存分析中，发现具有较高CaD表达的OSCC患者在疾病特异性生存和无病生存方面预后较差（分别为P=.003和P=.014）。多变量分析进一步表明，较高的CaD表达是疾病特异性生存的独立预测因子（P= 0.043）。口腔鳞癌患者血清钙调素水平明显升高，但与临床病理表现无关。从OEC-M1细胞中体外抑制，救援和过度表达钙调素获得的数据表明，钙调素促进迁移和侵袭过程中OSCC cell.CONCLUSIONSThe目前的研究结果共同表明，低分子量的钙调素在OSCC肿瘤的表达与肿瘤转移和患者生存。Cancer 2013;119：4003-4011. (c)2013年美国癌症协会
BACKGROUNDA 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.METHODSCaD 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.RESULTSCaD 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.CONCLUSIONSThe 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. (c) 2013 American Cancer Society.