Stage and tissue-specific prognostic impact of miR-182 in NSCLC.

Stage and tissue-specific prognostic impact of miR-182 in NSCLC.
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DOI:
10.1186/1471-2407-14-138
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发表时间:
2014-02-27
期刊:
影响因子:
3.8
通讯作者:
Bremnes RM
Bremnes RM
中科院分区:
医学2区
文献类型:
--
作者:
Stenvold H;Donnem T;Andersen S;Al-Saad S;Busund LT;Bremnes RM

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MicroRNA (miR)-182在癌症中经常上调,通常被视为一种致癌基因,可能与血管生成有关。我们旨在探讨miR-182在非小细胞肺癌(NSCLC)中的影响,并更明确地探讨其与血管生成标志物的相关性。从335例未选择的I至IIIA期非小细胞肺癌中,在组织微阵列块(tma)中收集了重复肿瘤和肿瘤相关基质核心。采用原位杂交(ISH)检测miR-182在肿瘤细胞中的表达,免疫组化(IHC)检测血管生成相关蛋白标志物的表达。在单因素分析中,miR-182的高肿瘤细胞表达是鳞状细胞癌(SCC, P = 0.042)和II期患者(P = 0.003)的积极预后因素。同样在多因素分析中,在同一组中,肿瘤细胞miR-182高表达与良好预后相关(SCC: HR 0.57, CI 95% 0.33-0.99, P = 0.048; II期:HR 0.50, CI 95% 0.28-0.90, P = 0.020)。我们发现miR-182与血管生成相关标志物FGF2、HIF2α和MMP-7之间存在显著相关性。在SCC患者和II期患者中,肿瘤细胞miR-182高表达是一个独立的阳性预后因素。
MicroRNA (miR)-182 is frequently upregulated in cancers, has generally been viewed as an oncogene and is possibly connected to angiogenesis. We aimed to explore what impact miR-182 has in non-small cell lung cancer (NSCLC), and more explicitly its correlation with angiogenic markers. From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarray blocks (TMAs). In situ hybridization (ISH) was used to detect the expression of miR-182 in tumor cells, and immunohistochemistry (IHC) was used to detect the expression of angiogenesis related protein markers. In univariate analyses, high tumor cell expression of miR-182 was a positive prognostic factor for patients with squamous cell carcinoma (SCC, P = 0.042) and stage II patients (P = 0.003). Also in the multivariate analysis, high tumor cell miR-182 expression was associated with a good prognosis in the same groups (SCC: HR 0.57, CI 95% 0.33-0.99, P = 0.048; stage II: HR 0.50, CI 95% 0.28-0.90, P = 0.020). We found significant correlations between miR-182 and the angiogenesis related markers FGF2, HIF2α and MMP-7. In patients with SCC and in stage II patients, high tumor cell miR-182 expression is an independent positive prognostic factor.
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