Identification of RAB2A and PRDX1 as the potential biomarkers for oral squamous cell carcinoma using mass spectrometry-based comparative proteomic approach
Identification of RAB2A and PRDX1 as the potential biomarkers for oral squamous cell carcinoma using mass spectrometry-based comparative proteomic approach
复制标题
DOI：
10.1007/s13277-015-3758-7
复制
发表时间：
2015-12-01
期刊：
影响因子：
--
通讯作者：
Mandal, Mahitosh
中科院分区：
文献类型：
--
作者：
Dey, Kaushik Kumar;Pal, Ipsita;Mandal, Mahitosh
尽管最近在诊断和治疗策略方面取得了进展，但口腔鳞状细胞癌（OSCC）仍然是一个主要的健康负担。蛋白质生物标志物的发现，早期发现将有助于提高患者的生存率在口腔鳞状细胞癌。基于质谱的蛋白质组学已成为检测各种类型癌症中蛋白质生物标志物的一种极好方法。在目前的研究中，我们已经使用4-异序相对和绝对定量（iTRAQ）为基础的鸟枪定量蛋白质组学方法，以确定蛋白质的差异表达的癌组织相比，正常组织。高分辨率质谱分析鉴定了2，074个蛋白质，其中288个蛋白质差异表达。此外，注意到与邻近的正常组织相比，在OSCC来源的癌组织样品中，162种蛋白质上调，而125种蛋白质下调。我们鉴定了一些已知的分子，如MMP-9（8.4倍），ZNF 142（5.6倍）和S100 A7（3.5倍），这些分子在OSCC中较早报道。除此之外，我们还发现了一些新的特征蛋白，这些蛋白在早期的口腔鳞状细胞癌中没有报道，包括ras相关蛋白Rab-2A亚型，RAB 2A（4.6倍）和过氧化物酶氧还蛋白-1，PRDX 1（2.2倍）。在OSCC中使用组织微阵列载玻片进行的基于细胞化学的验证分别显示了80%和68%的测试临床病例中RAB 2A和PRDX 1基因的过表达。这项研究不仅将作为候选生物标志物的资源，而且将有助于了解候选分子对疾病进展和治疗潜力的作用。
Despite the recent advances in diagnostic and therapeutic strategies, oral squamous cell carcinoma (OSCC) remains a major health burden. Protein biomarker discovery for early detection will help to improve patient survival rate in OSCC. Mass spectrometry-based proteomics has emerged as an excellent approach for detection of protein biomarkers in various types of cancers. In the current study, we have used 4-Plex isobaric tags for relative and absolute quantitation (iTRAQ)-based shotgun quantitative proteomic approach to identify proteins that are differentially expressed in cancerous tissues compared to normal tissues. The high-resolution mass spectrometric analysis resulted in identifying 2,074 proteins, among which 288 proteins were differentially expressed. Further, it was noticed that 162 proteins were upregulated, while 125 proteins were downregulated in OSCC-derived cancer tissue samples as compared to the adjacent normal tissues. We identified some of the known molecules which were reported earlier in OSCC such as MMP-9 (8.4-fold), ZNF142 (5.6-fold), and S100A7 (3.5-fold). Apart from this, we have also identified some novel signature proteins which have not been reported earlier in OSCC including ras-related protein Rab-2A isoform, RAB2A (4.6-fold), and peroxiredoxin-1, PRDX1 (2.2-fold). The immunohistochemistry-based validation using tissue microarray slides in OSCC revealed overexpression of the RAB2A and PRDX1 gene in 80 and 68 % of the tested clinical cases, respectively. This study will not only serve as a resource of candidate biomarkers but will contribute towards the existing knowledge on the role of the candidate molecules towards disease progression and therapeutic potential.