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HMGA1的高表达与非小细胞肺癌的恶性状态及预后相关。

Elevated expression of HMGA1 correlates with the malignant status and prognosis of non-small cell lung cancer.

作者信息

Zhang Ze, Wang Quan, Chen Feng, Liu Jun

机构信息

Norman Bethune Health Science Center, Jilin University, 130000, Changchun, Jilin, China.

出版信息

Tumour Biol. 2015 Feb;36(2):1213-9. doi: 10.1007/s13277-014-2749-4. Epub 2014 Oct 25.

DOI:10.1007/s13277-014-2749-4
PMID:25344216
Abstract

High-mobility group A1 (HMGA1) has been suggested to play a significant role in tumor progression, but little is known about the accurate significance of HMGA1 in non-small cell lung cancer (NSCLC) patients. The aim of this study was to identify the role of HMGA1 in NSCLC. The expression status of HMGA1 was observed initially in NSCLC by Gene Expression Omnibus (GEO). The expression of HMGA1 messenger RNA (mRNA) and protein was examined in NSCLC and adjacent normal lung tissues through real-time PCR and immunohistochemistry. Meanwhile, the relationship of HMGA1 expression levels with clinical features and prognosis of NSCLC patients was analyzed. In our results, HMGA1 was overexpressed in NSCLC tissues compared with adjacent normal lung tissues in microarray data (GSE19804). HMGA1 mRNA and protein expressions were markedly higher in NSCLC tissues than in normal lung tissues (P < 0.001 and P = 0.010, respectively). Using immunohistochemistry, high levels of HMGA1 protein were positively correlated with the status of clinical stage (I-II vs. III-IV, P < 0.001), T classification (T1-T vs. T3-T4, P = 0.003), N classification (N0N1 vs. N2-N3, P < 0.001), M classification (M0 vs. M1, P = 0.002), and differentiated degree (high or middle vs. low or undifferentiated, P = 0.003) in NSCLC. Patients with higher HMGA1 expression had a significantly shorter overall survival time than did patients with low HMGA1 expression. Multivariate analysis indicated that the level of HMGA1 expression was an independent prognostic factor (P < 0.001) for the survival of patients with NSCLC. In conclusion, HMGA1 plays an important role on NSCLC progression and prognosis and may act as a convictive biomarker for prognostic prediction.

摘要

高迁移率族蛋白A1(HMGA1)被认为在肿瘤进展中起重要作用,但关于HMGA1在非小细胞肺癌(NSCLC)患者中的准确意义知之甚少。本研究旨在确定HMGA1在NSCLC中的作用。首先通过基因表达综合数据库(GEO)观察NSCLC中HMGA1的表达状态。通过实时PCR和免疫组织化学检测NSCLC及相邻正常肺组织中HMGA1信使核糖核酸(mRNA)和蛋白的表达。同时,分析HMGA1表达水平与NSCLC患者临床特征及预后的关系。结果显示,在微阵列数据(GSE19804)中,与相邻正常肺组织相比,NSCLC组织中HMGA1过表达。NSCLC组织中HMGA1 mRNA和蛋白表达明显高于正常肺组织(分别为P < 0.001和P = 0.010)。采用免疫组织化学方法,NSCLC中高水平的HMGA1蛋白与临床分期(I-II期与III-IV期,P < 0.001)、T分级(T1-T2期与T3-T4期,P = 0.003)、N分级(N0-N1期与N2-N3期,P < 0.001)、M分级(M0期与M1期,P = 0.002)以及分化程度(高分化或中分化与低分化或未分化,P = 0.003)状态呈正相关。HMGA1表达较高的患者总生存时间明显短于HMGA1表达较低的患者。多因素分析表明,HMGA1表达水平是NSCLC患者生存的独立预后因素(P < 0.001)。总之,HMGA1在NSCLC进展和预后中起重要作用,可能作为一种有说服力的生物标志物用于预后预测。

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