联合检测Fascin与EGFR对食管鳞癌患者预后判断的价值

doi:10.3969/j.issn.1004-616x.2014.03.008

摘要/Abstract

摘要：

目的：研究联合检测食管鳞癌组织中Fascin与EGFR蛋白表达对食管鳞癌患者预后判断的价值。方法：取189例食管鳞癌蜡块组织标本制作组织芯片。采用免疫组织化学的方法，检测Fascin与EGFR蛋白的表达情况，采用SPSS 13.0软件分析其与临床病理指标及患者生存期的关系。结果：免疫组织化学检测结果表明，Fascin与EGFR蛋白在食管鳞癌组织中的高表达率分别为35.4%和56.1%，二者均高表达率为29.5%。临床指标相关性分析结果表明，癌细胞局部淋巴结转移者和未转移者的食管鳞癌组织EGFR蛋白阳性表达率分别为68.7%和49.6%，EGFR蛋白的表达与局部淋巴结转移显著相关(P=0.014)。Kaplan-Meier生存分析结果显示，Fascin或EGFR蛋白高表达的食管鳞癌患者5年生存率较低，而Fascin和EGFR蛋白二者均高表达的食管鳞癌患者5年生存率更低；相关性分析结果表明，在食管鳞癌组织中，Fascin与EGFR蛋白表达之间存在着显著的正相关关系(r =0.208，P=0.004)。多因素Cox回归分析结果表明，作为独立因子预警食管鳞癌患者预后不良，Fascin与EGFR联合检测的风险度为1.987，与Fascin的风险度1.852相比，未见明显升高。ROC曲线分析结果表明，与单独检测比较，联合检测Fascin和EGFR蛋白对判断食管鳞癌患者5年生存率的特异性明显升高。结论：食管鳞癌组织中Fascin与EGFR蛋白均高表达可能预示食管癌患者预后不良。

关键词: Fascin, EGFR, 食管鳞癌, 预后

Abstract:

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is still the leading cancer-caused mortality in China，and 5-year survival remains poor. The aim of this study is to survey the ability that coexpression of Fascin and EGFR predicts ESCC prognosis. METHODS：We collected 189 formalin-fixed paraffin-embedded esophageal curative resection specimens，and then constructed tissue microarray. Immunohistochemistry (IHC) was used for detecting the co-expression of Fascin and EGFR. Statistical analyses were performed using SPSS 13.0 for windows. RESULTS：Our IHC results showed that positive rates of high-expression of Fascin and EGFR were 35.4% and 56.1%，respectively. Positive rate of co-expression of Fascin and EGFR was 29.5%. The Kendall’s tau-b correlation analysis indicated that EGFR expression was associated with regional lymph node metastasis. Positive rate of EGFR without regional lymph node metastasis was 49.6%，while it was 68.7% with regional lymph node metastasis，P=0.014. Kaplan-Meier survival analysis showed that high-expression of Fascin and EGFR were associated with poor survival，while co-expression of Fascin and EGFR presented poorer survival. Pearson’s rank correlation analysis illustrated that there was a significant correlation between Fascin and EGFR. The multivariate Cox stepwise regression analysis demonstrated that Fascin/EGFR coexpression was a passive independent poor prognostic factor for overall survival. The RR for patients with high-coexpression of Fascin/EGFR was 1.987 ，just a little higher than RR for high-expression of Fascin. The ROC curve analysis indicated that the specificity of the combination of Fascin and EGFR was more robust than that of a single biomarker. CONCLUSION：This study has successfully showed that co-expression of Fascin and EGFR could confer a poor prognosis.

Key words: Fascin, EGFR, ESCC, prognosis

姚晓冬，曹卉慧，吴健谊，许秀娥，郑春鹏，沈金辉，王少洪，许丽艳，吴智勇. 联合检测Fascin与EGFR对食管鳞癌患者预后判断的价值[J]. 癌变·畸变·突变, doi: 10.3969/j.issn.1004-616x.2014.03.008.

YAO Xiao-dong，CAO Hui-hui，WU Jian-yi，XU Xiu-e，ZHENG Chun-peng，SHEN Jin-hui，WANG Shao-hong，XU Li-yan，WU Zhi-yong. Co-expression of Fascin and EGFR predicts esophageal squamous cell carcinoma prognosis[J]. Carcinogenesis, Teratogenesis & Mutagenesis, doi: 10.3969/j.issn.1004-616x.2014.03.008.

参考文献

[1] Xie JJ，Xu LY，Zhang HH，et al. Role of fascin in the proliferation and invasiveness of esophageal carcinoma cells[J]. Biochem Biophys Res Commun，2005，337(1)：355-362.

[2] Hashimoto Y，Ito T，Inoue H，et al. Prognostic significance of fascin overexpression in human esophageal squamous cell carcinoma[J]. Clin Cancer Res，2005，11(7)：2597-2605.

[3] Zhang H，Xu L，Xiao D，et al. Fascin is a potential biomarker for early-stage oesophageal squamous cell carcinoma[J]. J Clin Pathol，2006，59(9)：958-964.

[4] Xie JJ，Xu LY，Wu JY，et al. Involvement of CYR61 and CTGF in the fascin-mediated proliferation and invasiveness of esophageal squamous cell carcinomas cells[J]. Am J Pathol， 2010，176(2)：939-951.

[5] Hsu KF，Lin CK，Yu CP，et al. Cortactin，fascin，and survivin expression associated with clinicopathological parameters in esophageal squamous cell carcinoma[J]. Dis Esophagus， 2009，22(5)：402-408.

[6] Takikita M，Hu N，Shou JZ，et al. Fascin and CK4 as biomarkers for esophageal squamous cell carcinoma[J]. Anticancer Res，2011，31(3)：945-952.

[7] Lu XF，Li EM，Du ZP，et al. Specificity protein 1 regulates fascin expression in esophageal squamous cell carcinoma as the result of the epidermal growth factor/extracellular signal-regulated kinase signaling pathway activation[J]. Cell Mol Life Sci，2010，67(19)：3313-3329.

[8] Kureishy N，Sapountzi V，Prag S，et al. Fascins，and their roles in cell structure and function[J]. Bioessays，2002， 24(4)：350-361.

[9] Edwards RA，Bryan J. Fascins，a family of actin bundling proteins[J]. Cell Motil Cytoskeleton，1995，32(1)：1-9.

[10] Adams JC. Roles of fascin in cell adhesion and motility[J]. Curr Opin Cell Biol，2004，16(5)：590-596.

[11] Adams JC. Fascin protrusions in cell interactions[J]. Trends Cardiovasc Med，2004，14(6)：221-226.

[12] Jayo A，Parsons M. Fascin：a key regulator of cytoskeletal dynamics[J]. Int J Biochem Cell Biol，2010，42(10)：1614-1617.

[13] Friess H，Fukuda A，Tang WH，et al. Concomitant analysis of the epidermal growth factor receptor family in esophageal cancer：overexpression of epidermal growth factor receptor mRNA but not of c-erbB-2 and c-erbB-3[J]. World J Surg，1999，23(10)：1010-1018.

[14] Radojicic J，Zaravinos A，Spandidos DA. HPV，KRAS mutations，alcohol consumption and tobacco smoking effects on esophageal squamous-cell carcinoma carcinogenesis[J]. Int J Biol Markers，2012，27(1)：1-12.

[15] Tetreault MP，Wang ML，Yang Y，et al. Klf4 overexpression activates epithelial cytokines and inflammation-mediated esophageal squamous cell cancer in mice[J]. Gastroenterology， 2010，139(6)：2124-2134.

[16] Bird-Lieberman EL，Fitzgerald RC. Early diagnosis of oesophageal cancer[J]. Br J Cancer，2009，101(1)：1-6.