Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer.
Prognostic impact of alternative splicing-derived hMENA isoforms in resected, node-negative, non-small-cell lung cancer.
复制标题
DOI：
10.18632/oncotarget.2609
复制
发表时间：
2014-11-30
期刊：
影响因子：
--
通讯作者：
Nisticò P
中科院分区：
文献类型：
--
作者：
Bria E;Di Modugno F;Sperduti I;Iapicca P;Visca P;Alessandrini G;Antoniani B;Pilotto S;Ludovini V;Vannucci J;Bellezza G;Sidoni A;Tortora G;Radisky DC;Crinò L;Cognetti F;Facciolo F;Mottolese M;Milella M;Nisticò P
风险评估和治疗选择仍然是早期非小细胞肺癌（NSCLC）的一个挑战。选择性剪接是诊断、预后和治疗工具的新兴来源。在此，我们研究了肌动蛋白细胞骨架调节因子hMENA及其亚型hMENA 11 a和hMENAΔv6在早期NSCLC中的预后价值。上皮hMENA 11 a亚型在表达E-CADHERIN的NSCLC细胞系中表达，并与hMENAΔv6交替表达。hMENAΔv6或hMENA 11 a的增强表达分别增加或降低A549细胞的侵袭能力。在248例淋巴结阴性NSCLC中评估hMENA同种型表达。在多变量分析中，高泛hMENA和低hMENA 11 a是无病生存期和癌症特异性生存期较短的唯一独立预测因子，低hMENA 11 a是总生存期较短的独立预测因子。低泛hMENA/高hMENA 11 a表达的患者的表现显著优于任何其他亚组（P≤0.0015）。这种混合变量与T大小和切除的淋巴结数量一起纳入3级风险分层模型，该模型显着区分了复发、癌症相关死亡和死亡的不同风险。该模型在133名患者的独立数据集中进行了外部验证。hMENA剪接异构体的相对表达是早期NSCLC的一个强有力的预后因素，补充了临床参数，以准确预测个体患者的风险。
Risk assessment and treatment choice remain a challenge in early non-small-cell lung cancer (NSCLC). Alternative splicing is an emerging source for diagnostic, prognostic and therapeutic tools. Here, we investigated the prognostic value of the actin cytoskeleton regulator hMENA and its isoforms, hMENA11a and hMENAΔv6, in early NSCLC. The epithelial hMENA11a isoform was expressed in NSCLC lines expressing E-CADHERIN and was alternatively expressed with hMENAΔv6. Enforced expression of hMENAΔv6 or hMENA11a increased or decreased the invasive ability of A549 cells, respectively. hMENA isoform expression was evaluated in 248 node-negative NSCLC. High pan-hMENA and low hMENA11a were the only independent predictors of shorter disease-free and cancer-specific survival, and low hMENA11a was an independent predictor of shorter overall survival, at multivariate analysis. Patients with low pan-hMENA/high hMENA11a expression fared significantly better (P≤0.0015) than any other subgroup. Such hybrid variable was incorporated with T-size and number of resected lymph nodes into a 3-class-risk stratification model, which strikingly discriminated between different risks of relapse, cancer-related death, and death. The model was externally validated in an independent dataset of 133 patients. Relative expression of hMENA splice isoforms is a powerful prognostic factor in early NSCLC, complementing clinical parameters to accurately predict individual patient risk.
登录
查看更多内容
预测切除非鳞状非小细胞肺癌生存率的实用分子测定：开发和国际验证研究
影响因子：
168.9
作者：
Kratz, Johannes R.;He, Jianxing;Van den Eeden, Stephen K.;Zhu, Zhi-Hua;Gao, Wen;Pham, Patrick T.;Mulvihill, Michael S.;Ziaei, Fatemeh;Zhang, Huanrong;Su, Bo;Zhi, Xiuyi;Quesenberry, Charles P.;Habel, Laurel A.;Deng, Qiuhua;Wang, Zongfei;Zhou, Jiangfen;Li, Huiling;Huang, Mei-Chun;Yeh, Che-Chung;Segal, Mark R.;Ray, M. Roshni;Jones, Kirk D.;Raz, Dan J.;Xu, Zhidong;Jahan, Thierry M.;Berryman, David;He, Biao;Mann, Michael J.;Jablons, David M.
通讯作者：
Jablons, David M.
影响因子：
64.5
作者：
Gertler, FB;Niebuhr, K;Soriano, P
通讯作者：
Soriano, P
DOI：
10.1073/pnas.1214394109
发表时间：
2012-11-20
影响因子：
11.1
作者：
Di Modugno, Francesca;Iapicca, Pierluigi;Nistico, Paola
通讯作者：
Nistico, Paola
影响因子：
2
作者：
SAUERBREI, W;SCHUMACHER, M
通讯作者：
SCHUMACHER, M
影响因子：
10.3
作者：
Chen, Dung-Tsa;Hsu, Ying-Lin;Cress, W. Douglas
通讯作者：
Cress, W. Douglas