Tian Wen-Dong, Li Jun-Zheng, Hu Shui-Wang, Peng Xiao-Wei, Li Gang, Liu Xiong, Chen Huai-Hong, Xu Xia, Li Xiang-Ping
Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China.
Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University Guangzhou 510515, Guangdong, China ; Department of Otolaryngology-Head and Neck Surgery, The Fifth People's Hospital of Dongguan Dongguan 523905, Guangdong, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9021-31. eCollection 2015.
Hypopharyngeal squamous cell carcinoma (HSCC) has very poor prognosis compared with other head and neck squamous cell carcinomas. Late-stage diagnosis of HSCC increases mortality. Therefore, more effective biomarkers for early diagnosis of HSCC are necessary. Unfortunately, appropriate biomarkers for clinical diagnosis and prognosis have not been identified yet. However, recent progresses in quantitative proteomics have offered opportunities to identify plasma proteins as biomarkers for HSCC. In the present study, plasma samples were analyzed by two-dimensional differential gel electrophoresis (2D-DIGE), and differentially expressed proteins were identified by matrix assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF MS). A total of 26 proteins representing 12 unique gene products were identified. The up-regulation proteins were alpha-2-HS-glycoprotein (AHSG), complement C4-B, haptoglobin, C-reactive protein, and ceruloplasmin, whereas the down-regulation proteins were serum albumin, angiotensinogen, alpha-1-antichymotrypsin, Ig gamma-3 chain C region, fibrinogen gamma chain, apolipoprotein A-I, and Ig kappa chain C region. Among all the differentially expressed proteins, AHSG was validated by western blot and ELISA. The results were consistent with the data from 2D-DIGE, further suggesting that AHSG may be employed as a potential biomarker for the early diagnosis of HSCC. In summary, this study was the first to use 2D-DIGE and MALDI-TOF/TOF platform to identify the potential plasma biomarkers for HSCC. The plasma AHSG showed great potential for HSCC screening.
下咽鳞状细胞癌（HSCC）与其他头颈部鳞状细胞癌相比预后很差。HSCC的晚期诊断会增加死亡率。因此，需要更有效的生物标志物用于HSCC的早期诊断。不幸的是，尚未确定用于临床诊断和预后的合适生物标志物。然而，定量蛋白质组学的最新进展为鉴定血浆蛋白作为HSCC的生物标志物提供了机会。在本研究中，通过二维差异凝胶电泳（2D-DIGE）分析血浆样本，并通过基质辅助激光解吸电离飞行时间/飞行时间质谱（MALDI-TOF/TOF MS）鉴定差异表达的蛋白质。共鉴定出代表12种独特基因产物的26种蛋白质。上调的蛋白质是α-2-HS-糖蛋白（AHSG）、补体C4-B、触珠蛋白、C反应蛋白和铜蓝蛋白，而下调的蛋白质是血清白蛋白、血管紧张素原、α-1-抗糜蛋白酶、Igγ-3链C区、纤维蛋白原γ链、载脂蛋白A-I和Igκ链C区。在所有差异表达的蛋白质中，AHSG通过蛋白质免疫印迹和酶联免疫吸附测定进行了验证。结果与2D-DIGE的数据一致，进一步表明AHSG可能用作HSCC早期诊断的潜在生物标志物。总之，本研究首次使用2D-DIGE和MALDI-TOF/TOF平台鉴定HSCC的潜在血浆生物标志物。血浆AHSG在HSCC筛查中显示出巨大潜力。
