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应用组织微阵列检测磷酸化信号转导和转录激活因子 3、表皮生长因子受体、p53 和血管内皮生长因子受体 1 在切除的肺腺癌中的表达对临床的影响。

Clinical impact of phosphorylated signal transducer and activator of transcription 3, epidermal growth factor receptor, p53, and vascular endothelial growth factor receptor 1 expression in resected adenocarcinoma of lung by using tissue microarray.

机构信息

Division of Hematology and Oncology, Department of Internal Medicine, Hallym University Medical Center, Hallym University College of Medicine, Seoul, Korea.

出版信息

Cancer. 2010 Feb 1;116(3):676-85. doi: 10.1002/cncr.24748.

Abstract

BACKGROUND

The signal transducer and activator of transcription 3 (STAT3) play a key role in the downstream pathway of the epidermal growth factor receptor (EGFR) in nonsmall cell lung cancer and promote cell proliferation, invasion, and angiogenesis. The clinical significance of phosphorylated STAT3 (pSTAT3), EGFR, p53, and vascular endothelial growth factor receptor 1 (VEGFR-1) expression in patients with completely resected lung adenocarcinoma was evaluated to determine the effects of pSTAT3 in tumor angiogenesis and proliferation.

METHODS

The expressions of pSTAT3, EGFR, p53, and VEGFR-1 were evaluated by immunohistochemical staining of tissue microarrays from 162 samples of resected lung adenocarcinoma.

RESULTS

The median age of the 162 patients was 62 years, the median disease-free survival was 41.7 months, and the median OS (OS) was 80.2 months. Expression of pSTAT3, EGFR, p53, and VEGFR-1 was detected in 51.2%, 71%, 35.2%, and 35.2% of the samples, respectively. pSTAT3 expression was correlated significantly with VEGFR-1 expression (P = .025). The coexpression of pSTAT3 and VEGFR-1 was correlated with increased lymph node involvement (P = .021) and a trend toward a short OS (P = .085). In multivariate analysis, the expression levels of p53 and VEGFR-1 were identified as independent prognostic factors that affected OS.

CONCLUSIONS

The results of this study suggested that pSTAT3 and VEGFR-1 expression may play roles in the tumor progression and angiogenesis of lung adenocarcinoma. Further studies are needed, however, to uncover the detailed mechanisms that underlie the roles of these proteins in lung adenocarcinoma.

摘要

背景

信号转导子和转录激活子 3(STAT3)在非小细胞肺癌中表皮生长因子受体(EGFR)的下游途径中发挥关键作用,并促进细胞增殖、侵袭和血管生成。评估完全切除的肺腺癌患者中磷酸化 STAT3(pSTAT3)、EGFR、p53 和血管内皮生长因子受体 1(VEGFR-1)表达的临床意义,以确定 pSTAT3 在肿瘤血管生成和增殖中的作用。

方法

通过对 162 例切除的肺腺癌组织微阵列进行免疫组织化学染色,评估 pSTAT3、EGFR、p53 和 VEGFR-1 的表达。

结果

162 例患者的中位年龄为 62 岁,无病生存期的中位数为 41.7 个月,总生存期(OS)的中位数为 80.2 个月。pSTAT3、EGFR、p53 和 VEGFR-1 的表达在 51.2%、71%、35.2%和 35.2%的样本中分别被检测到。pSTAT3 的表达与 VEGFR-1 的表达显著相关(P =.025)。pSTAT3 和 VEGFR-1 的共表达与淋巴结受累增加相关(P =.021),并且与 OS 缩短呈趋势相关(P =.085)。多变量分析显示,p53 和 VEGFR-1 的表达水平是影响 OS 的独立预后因素。

结论

本研究结果表明,pSTAT3 和 VEGFR-1 的表达可能在肺腺癌的肿瘤进展和血管生成中发挥作用。然而,需要进一步的研究来揭示这些蛋白在肺腺癌中作用的详细机制。

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