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哺乳动物雷帕霉素靶蛋白(mTOR)过表达和血管侵犯是早期 NSCLC 的不良预后因素:一项验证性研究。

Overexpression of the mammalian target of rapamycin (mTOR) and angioinvasion are poor prognostic factors in early stage NSCLC: a verification study.

机构信息

Thoracic Oncology Research Group, Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.

出版信息

Lung Cancer. 2012 Feb;75(2):217-22. doi: 10.1016/j.lungcan.2011.06.012. Epub 2011 Jul 30.

Abstract

BACKGROUND

A recent study by Dhillon et al. [12], identified both angioinvasion and mTOR as prognostic biomarkers for poor survival in early stage NSCLC. The aim of this study was to verify the above study by examining the angioinvasion and mTOR expression profile in a cohort of early stage NSCLC patients and correlate the results to patient clinico-pathological data and survival.

METHODS

Angioinvasion was routinely recorded by the pathologist at the initial assessment of the tumor following resection. mTOR was evaluated in 141 early stage (IA-IIB) NSCLC patients (67 - squamous; 60 - adenocarcinoma; 14 - others) using immunohistochemistry (IHC) analysis with an immunohistochemical score (IHS) calculated (% positive cells×staining intensity). Intensity was scored as follows: 0 (negative); 1+ (weak); 2+ (moderate); 3+ (strong). The range of scores was 0-300. Based on the previous study a cut-off score of 30 was used to define positive versus negative patients. The impact of angioinvasion and mTOR expression on prognosis was then evaluated.

RESULTS

101 of the 141 tumors studied expressed mTOR. There was no difference in mTOR expression between squamous cell carcinoma and adenocarcinoma. Angioinvasion (p=0.024) and mTOR staining (p=0.048) were significant univariate predictors of poor survival. Both remained significant after multivariate analysis (p=0.037 and p=0.020, respectively).

CONCLUSIONS

Our findings verify angioinvasion and mTOR expression as new biomarkers for poor outcome in patients with early stage NSCLC. mTOR expressing patients may benefit from novel therapies targeting the mTOR survival pathway.

摘要

背景

最近,Dhillon 等人的一项研究[12]确定了血管侵犯和 mTOR 均为早期 NSCLC 患者生存预后不良的预测生物标志物。本研究旨在通过检查早期 NSCLC 患者的血管侵犯和 mTOR 表达谱,并将结果与患者临床病理数据和生存相关联,来验证上述研究。

方法

在肿瘤切除后的初始评估中,病理学家常规记录血管侵犯情况。使用免疫组织化学(IHC)分析评估 141 例早期(IA-IIB)NSCLC 患者(67 例为鳞状细胞癌;60 例为腺癌;14 例为其他类型)的 mTOR 表达情况,通过免疫组化评分(IHS)计算(阳性细胞百分比×染色强度)。强度评分如下:0(阴性);1+(弱阳性);2+(中度阳性);3+(强阳性)。评分范围为 0-300。根据之前的研究,将 30 分作为阳性与阴性患者的分界值。然后评估血管侵犯和 mTOR 表达对预后的影响。

结果

在研究的 141 例肿瘤中,有 101 例表达 mTOR。鳞状细胞癌和腺癌之间的 mTOR 表达没有差异。血管侵犯(p=0.024)和 mTOR 染色(p=0.048)是生存不良的单变量显著预测因子。多变量分析后两者仍然具有显著意义(p=0.037 和 p=0.020)。

结论

我们的研究结果验证了血管侵犯和 mTOR 表达是早期 NSCLC 患者预后不良的新生物标志物。表达 mTOR 的患者可能受益于针对 mTOR 生存通路的新型治疗方法。

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