Protein clusters associated with carcinogenesis, histological differentiation and nodal metastasis in esophageal cancer

Protein clusters associated with carcinogenesis, histological differentiation and nodal metastasis in esophageal cancer
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DOI:
10.1002/pmic.200600488
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发表时间:
2006-12-01
期刊:
影响因子:
3.4
通讯作者:
Hirohashi, Setsuo
Hirohashi, Setsuo
中科院分区:
生物学3区
文献类型:
--
作者:
Hatakeyama, Hiromitsu;Kondo, Tadashi;Hirohashi, Setsuo

文献摘要

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我们研究了食管癌的蛋白质组背景。我们采用激光显微切割技术从72例食管鳞状细胞癌中获取肿瘤组织,并在其中57例中获取癌旁正常组织。2D-DIGE产生了1730个蛋白质点的定量表达谱。基于蛋白质斑点的强度,非监督分类将肿瘤组织与其正常对应物区分开,并根据其组织学分化将肿瘤组织细分。我们在肿瘤组织中鉴定了498个强度改变的蛋白质点,通过LC-MS/MS的蛋白质鉴定显示对应于217个基因产物。我们还发现了41个与淋巴结转移相关的蛋白质点,并鉴定了33个与这些点相对应的蛋白质,包括癌症相关蛋白,如α-辅肌动蛋白4、hnRNP K、periplakin、鳞状细胞癌抗原1和NudC。先前已经报道了所鉴定的癌症相关蛋白单独参与一系列癌症类型,并且我们的研究在单一类型的恶性肿瘤食管癌中集体观察到它们。由于这些蛋白质参与了细胞骨架/结构组织、转运、伴侣、氧化还原、转录和信号转导等重要的生物学过程,因此它们可能在食管癌的发生和发展过程中发挥协同作用。
We examined the proteomic background of esophageal cancer. We used laser microdissection to obtain tumor tissues from 72 esophageal squamous cell carcinoma cases and adjacent normal tissues in 57 of these cases. The 2D-DIGE generated quantitative expression profiles with 1730 protein spots. Based on the intensity of the protein spots, unsupervised classification distinguished the tumor tissues from their normal counterparts, and subdivided the tumor tissues according to their histological differentiation. We identified 498 protein spots with altered intensity in the tumor tissues, which protein identification by LC-MS/MS showed to correspond to 217 gene products. We also found 41 protein spots that were associated with nodal metastasis, and identified 33 proteins corresponding to the spots, including cancer-associated proteins such as alpha-actinin 4, hnRNP K, periplakin,squamous cell carcinoma antigen 1 and NudC. The identified cancer-associated proteins have been previously reported to be individually involved in a range of cancer types, and our study observed them collectively in a single type of malignancy, esophageal cancer. As the identified proteins are involved in important biological processes such as cytoskeletal/structural organization, transportation, chaperon, oxidoreduction, transcription and signal transduction, they may function in a coordinate manner in carcinogenesis and tumor progression of esophageal cancer.