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通过对肿瘤微环境间质液进行蛋白质组分析确定,Fascin是一种用于头颈癌的循环肿瘤标志物。

Fascin is a circulating tumor marker for head and neck cancer as determined by a proteomic analysis of interstitial fluid from the tumor microenvironment.

作者信息

Lee Li-Yu, Chen Yin-Ju, Lu Ya-Ching, Liao Chun-Ta, Chen I-How, Chang Joseph Tung-Chieh, Huang Yu-Chen, Chen Wen-Ho, Huang Chi-Che, Tsai Chi-Ying, Cheng Ann-Joy

出版信息

Clin Chem Lab Med. 2015 Sep 1;53(10):1631-41. doi: 10.1515/cclm-2014-1016.

Abstract

BACKGROUND

Head and neck cancer (HNC) is a prevalent cancer worldwide; however, clinically useful tumor markers for HNC have not been identified. Here, we aimed to identify secretory proteins from the tumor microenvironment as candidate circulating tumor markers.

METHODS

Samples derived from seven pairs of tumor interstitial fluid (TIF) and normal interstitial fluid (NIF) samples from patients with HNC were analyzed. The proteomes were determined by gel-based-mass-spectrometry proteomic methods. The most up-regulated protein, fascin was confirmed in the cancer tissues and cell culture supernatant by immunoblotting and immunohistochemistry assays. Serum fascin was determined in 40 HNC and 40 normal individuals by ELISA.

RESULTS

After proteomics analysis, 189 peptides were identified, corresponding to 75 proteins. Of the 21 proteins which were identified more than twice, five up-regulated proteins identified most frequently including fascin. The most elevated fascin was over-expressed in cancer tissues and cell culture supernatant. Serum fascin was significantly up-regulated in the cancer patients (p<0.001) and correlated with pathological lymph node metastasis (p=0.022). To assess the diagnostic efficacy, serum levels of fascin and another potential biomarker SCCA were determined. Fascin showed a high predictable value with an area under the curve (AUC) of 0.808 (95% CI 0.723-0.901) in the receiver operator curve (ROC), compared to 0.501 (95% CI 0.378-0.634) for SCCA.

CONCLUSIONS

We have identified 75 potential circulating tumor markers associated with HNC, including fascin. Serum fascin could discriminate cancer patients from healthy individuals; thus, it may serve as a circulating biomarker for HNC.

摘要

背景

头颈癌(HNC)是全球范围内一种常见的癌症;然而,尚未确定对HNC具有临床实用价值的肿瘤标志物。在此,我们旨在从肿瘤微环境中鉴定分泌蛋白作为候选循环肿瘤标志物。

方法

分析了来自7例HNC患者的肿瘤间质液(TIF)和正常间质液(NIF)样本对。通过基于凝胶的质谱蛋白质组学方法测定蛋白质组。通过免疫印迹和免疫组织化学分析在癌组织和细胞培养上清液中证实了上调最明显的蛋白质fascin。通过酶联免疫吸附测定法(ELISA)测定了40例HNC患者和40例正常个体的血清fascin。

结果

经过蛋白质组学分析,鉴定出189个肽段,对应75种蛋白质。在被鉴定出不止两次的21种蛋白质中,有5种上调最频繁的蛋白质,包括fascin。上调最明显的fascin在癌组织和细胞培养上清液中过度表达。癌患者血清fascin显著上调(p<0.001),并与病理淋巴结转移相关(p=0.022)。为评估诊断效能,测定了fascin和另一种潜在生物标志物鳞状细胞癌抗原(SCCA)的血清水平。在受试者工作特征曲线(ROC)中,fascin显示出较高的预测价值,曲线下面积(AUC)为0.808(95%可信区间0.723 - 0.901),而SCCA的AUC为0.501(95%可信区间0.378 - 0.634)。

结论

我们已鉴定出75种与HNC相关的潜在循环肿瘤标志物,包括fascin。血清fascin可区分癌症患者与健康个体;因此,它可能作为HNC的循环生物标志物。

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