Comparative proteomic approach identifies PKM2 and cofilin-1 as potential diagnostic, prognostic and therapeutic targets for pulmonary adenocarcinoma.
Comparative proteomic approach identifies PKM2 and cofilin-1 as potential diagnostic, prognostic and therapeutic targets for pulmonary adenocarcinoma.
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比较蛋白质组学方法将 Pkm2 和 Cofilin-1 确定为肺腺癌的潜在诊断、预后和治疗靶点
DOI：
10.1371/journal.pone.0027309
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tong AP
中科院分区：
文献类型：
--
作者：
Peng XC;Gong FM;Zhao YW;Zhou LX;Xie YW;Liao HL;Lin HJ;Li ZY;Tang MH;Tong AP
肺癌是世界上癌症相关死亡的主要原因。非小细胞肺癌（Non-SCLC）占肺癌的近80%，其中40%为腺癌。为了更好地了解肺癌，特别是肺腺癌发生发展的分子机制，我们利用蛋白质组学技术寻找肺腺癌的候选预后和治疗靶点。应用双向聚丙烯酰胺凝胶电泳（2-DE）技术，分析人肺腺癌组织与其癌旁正常组织蛋白质表达谱的变化。用ESI-Q-TOF MS/MS鉴定差异表达蛋白质点。结果，在肺腺癌中鉴定出32个差异表达蛋白（超过2倍，p<0.05）。其中，两个蛋白质（PKM 2和cofilin-1），在腺癌中显着上调，被选为详细的分析。免疫组化结果显示PKM 2和cofilin-1的表达与上皮异型增生的严重程度及预后相关。RNA干扰抑制PKM 2表达可显著抑制肺腺癌SPC-A1细胞的体外生长和诱导凋亡，抑制肺腺癌SPC-A1细胞的体内移植瘤生长（P<0.05）。此外，靶向cofilin-1的shRNA表达质粒在LL/2转移模型中显著抑制肿瘤转移并延长生存期。虽然需要进一步的工作来阐明这些改变的蛋白质的生物学意义和分子机制，但PKM 2和cofilin-1可能作为肺腺癌的潜在诊断和预后生物标志物以及治疗靶点。
Lung cancer is the leading cause of cancer-related death in the world. Non-small cell lung carcinomas (Non-SCLC) account for almost 80% of lung cancers, of which 40% were adenocarcinomas. For a better understanding of the molecular mechanisms behind the development and progression of lung cancer, particularly lung adenocarcinoma, we have used proteomics technology to search for candidate prognostic and therapeutic targets in pulmonary adenocarcinoma. The protein profile changes between human pulmonary adenocarcinoma tissue and paired surrounding normal tissue were analyzed using two-dimensional polyacrylamide gel electrophoresis (2-DE) based approach. Differentially expressed protein-spots were identified with ESI-Q-TOF MS/MS instruments. As a result, thirty two differentially expressed proteins (over 2-fold, p<0.05) were identified in pulmonary adenocarcinoma compared to normal tissues. Among them, two proteins (PKM2 and cofilin-1), significantly up-regulated in adenocarcinoma, were selected for detailed analysis. Immunohistochemical examination indicated that enhanced expression of PKM2 and cofilin-1 were correlated with the severity of epithelial dysplasia, as well as a relatively poor prognosis. Knockdown of PKM2 expression by RNA interference led to a significant suppression of cell growth and induction of apoptosis in pulmonary adenocarcinoma SPC-A1 cells in vitro, and tumor growth inhibition in vivo xenograft model (P<0.05). In addition, the shRNA expressing plasmid targeting cofilin-1 significantly inhibited tumor metastases and prolonged survival in LL/2 metastatic model. While additional works are needed to elucidate the biological significance and molecular mechanisms of these altered proteins identified in this study, PKM2 and cofilin-1 may serve as potential diagnostic and prognostic biomarkers, as well as therapeutic targets for pulmonary adenocarcinoma.
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影响因子：
82.9
作者：
Beer, DG;Kardia, SLR;Hanash, S
通讯作者：
Hanash, S
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Sánchez-Carbayo M