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Clinical significance of comprehensive expression analysis of cancer-related protein in non-small cell lung cancer using tissue microarray technology

应用组织芯片技术综合分析非小细胞肺癌肿瘤相关蛋白表达的临床意义

基本信息

批准号：
14571294
负责人：
MITSUDOMI Tetsuya
金额：
$ 2.24万
依托单位：
Aichi Cancer Center Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

First, we made TMA containing 976 cases of lung cancers and confirmed its validity by comparing the results obtained by the TMA with those by regular slides or mRNA expression experiments.Using TMA from 241 lung cancer patients, we analyzed expression of p53, p27, RB, EGFR, Bcl2, Synaptophysin, CD56 and TTF1 for their potential prognostic implication. However, only TTF1 showed a marginal prognostic impact among these markers.Thyroid transcription factor (TTF) 1 was expressed throughout the developmental stage of peripheral lung as well as 72% of pulmonary adenocarcinoma, suggesting that TTF1 could serve as a lineage marker of the peripheral lung. In contrast, expression of maspin, which is thought to be involved in motility or invasion of cancer cells, is inversely correlated with TTF1 expression, suggesting that this molecule is related to development of central airway.14-3-3sigma expression was examined in a spectrum of neuroendocrine lung tumors. Most of the tumors belonging to all the four categories of neuroendocrine lung tumors (i.e., carcinoid, atypical carcinoid, neuroendocrine large cell carcinoma, small cell carcinoma) lost expression of 14-3-3sigma in neuroendocrine differentiation.In summary, TMA allowed us rapid evaluation of expression of a given protein in many samples in the same experimental condition, which was very useful for analysis of molecular pathogenesis of lung cancer.

首先，我们制作了976例肺癌组织的TMA，并将其结果与常规切片或mRNA表达实验进行了比较，以证实TMA的有效性，同时对241例肺癌组织的TMA进行了p53、p27、RB、EGFR、Bcl 2、Synaptophysin、CD 56和TTF 1的表达分析，以探讨其潜在的预后意义。甲状腺转录因子1（TTF 1）在周围型肺的整个发育过程中都有表达，在72%的肺腺癌中也有表达，提示TTF 1可作为周围型肺的一个谱系标志物。与此相反，maspin，这被认为是参与运动或癌细胞的侵袭，表达与TTF 1的表达呈负相关，这表明该分子与中央气道的发展。14 -3-3sigma的表达进行了检查，在一个频谱的神经内分泌肺肿瘤。属于所有四类神经内分泌肺肿瘤的大多数肿瘤（即，结果表明，在神经内分泌分化过程中，14-3-3sigma蛋白在肺癌组织（包括类癌、非典型类癌、神经内分泌大细胞癌、小细胞癌）中表达缺失，TMA可在相同的实验条件下快速检测同一蛋白在多个样本中的表达，这对肺癌分子发病机制的分析具有重要意义。