Prognostic impacts of angiopoietins in NSCLC tumor cells and stroma: VEGF-A impact is strongly associated with Ang-2.
Prognostic impacts of angiopoietins in NSCLC tumor cells and stroma: VEGF-A impact is strongly associated with Ang-2.
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DOI：
10.1371/journal.pone.0019773
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Bremnes RM
中科院分区：
文献类型：
--
作者：
Andersen S;Donnem T;Al-Shibli K;Al-Saad S;Stenvold H;Busund LT;Bremnes RM
血管生成素及其受体Tie-2与VEGF-A一起是血管生成中的关键介质。本研究评估了所有已知的人血管生成素（Ang-1、Ang-2和Ang-4）及其受体Tie-2的预后影响，以及它们与VEGF-A的预后表达的关系。包括335名I-IIIA期NSCLC患者，并在组织微阵列（TMA）中收集相应肿瘤细胞和基质的组织样品。免疫组化（IHC）用于半定量评估重复肿瘤和间质核心中标志物的表达。在单变量分析中，肿瘤细胞低表达的Ang-4（P = 0.046）和基质低表达的Ang-4（P = 0.009）和Ang-2（P = 0.017）分别与较差的生存率相关。 在多变量分析中，低基质Ang-2（HR 1.88; CI 95% 1.15 - 3.08）和Ang-4（HR 1.47，CI 95% 1.02 - 2.11，P = 0.04）表达与不良预后独立相关。 在肿瘤细胞Ang-2高表达的患者中，伴随的肿瘤VEGF-A高表达介导了生存率的显着降低（P <0.001）。在多因素分析中，肿瘤血管内皮生长因子A高表达与血管紧张素2高表达的关系不密切（HR 6.43，95% CI 2.46-16.8，P <0.001）。在肿瘤细胞中，只有Ang-4表达对NSCLC的预后有影响。在肿瘤间质中，Ang-4和Ang-2独立地与存活相关。NSCLC中肿瘤细胞VEGF-A的预后影响似乎与伴随的高肿瘤细胞Ang-2表达强烈相关。
Angiopoietins and their receptor Tie-2 are, in concert with VEGF-A, key mediators in angiogenesis. This study evaluates the prognostic impact of all known human angiopoietins (Ang-1, Ang-2 and Ang-4) and their receptor Tie-2, as well as their relation to the prognostic expression of VEGF-A. 335 unselected stage I-IIIA NSCLC-patients were included and tissue samples of respective tumor cells and stroma were collected in tissue microarrays (TMAs). Immunohistochemistry (IHC) was used to semiquantitatively evaluate the expression of markers in duplicate tumor and stroma cores. In univariate analyses, low tumor cell expression of Ang-4 (P = 0.046) and low stromal expressions of Ang-4 (P = 0.009) and Ang-2 (P = 0.017) were individually associated with a poor survival. In the multivariate analysis, low stromal Ang-2 (HR 1.88; CI 95% 1.15-3.08) and Ang-4 (HR 1.47, CI 95% 1.02–2.11, P = 0.04) expressions were independently associated with a poor prognosis. In patients with high tumor cell expression of Ang-2, a concomitantly high tumor VEGF-A expression mediated a dramatic survival reduction (P<0.001). In the multivariate analysis of patients with high Ang-2 expression, high tumor VEGF-A expression appeared an independent poor prognosticator (HR 6.43; CI 95% 2.46–16.8; P<0.001). In tumor cells, only Ang-4 expression has prognostic impact in NSCLC. In tumor stroma, Ang-4 and Ang-2 are independently associated with survival. The prognostic impact of tumor cell VEGF-A in NSCLC appears strongly associated with a concomitantly high tumor cell expression of Ang-2.
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影响因子：
254.7
作者：
Jemal, Ahmedin;Siegel, Rebecca;Thun, Michael J.
通讯作者：
Thun, Michael J.
影响因子：
2.5
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2.5
作者：
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通讯作者：
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影响因子：
6.4
作者：
Nakayama, T;Yoshizaki, A;Sekine, I
通讯作者：
Sekine, I