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长链非编码 RNA HOTAIR 在子宫内膜癌中上调,并与不良预后相关。

The long non-coding RNA HOTAIR is upregulated in endometrial carcinoma and correlates with poor prognosis.

机构信息

International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200030, P.R. China.

Department of Obstetrics and Gynecology, Shanghai First People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201620, P.R. China.

出版信息

Int J Mol Med. 2014 Feb;33(2):325-32. doi: 10.3892/ijmm.2013.1570. Epub 2013 Nov 27.

DOI:10.3892/ijmm.2013.1570
PMID:24285342
Abstract

Long non-coding RNAs (lncRNAs) are emerging as key molecules in human cancer. Homeobox (HOX) transcript antisense intergenic RNA (HOTAIR), a long non-coding RNA (lncRNA), is associated with a variety of human cancers, such as breast, liver and lung cancer. However, whether HOTAIR can function as a molecular marker in endometrial carcinoma (EC) remains unknown. In the present study, the expression of HOTAIR in 66 EC tissues from patients with EC and 30 normal tissues from healthy age-matched control subjects was determined using quantitative reverse transcription PCR. Furthermore, using in situ hybridization, we measured HOTAIR expression in 129 formalin-fixed paraffin-embedded (FFPE) tissue sections, which included 96 tissues that matched the frozen cases, 21 other EC tissues and 12 atypical hyperplasia tissues. Correlations between HOTAIR expression and the clinicopathological characteristics of patients were analyzed. Our results revealed that HOTAIR expression in the EC tissues was significantly upregulated compared with normal tissues (p<0.001). In addition, we observed a significant association between HOTAIR expression and the EC grade (p<0.05) and lymph node metastasis (p<0.05). Moreover, in the FFPE tissues, but not the frozen tissues, we found that a higher HOTAIR expression also correlated with the depth of myometrial invasion (p=0.019) and lymphovascular space invasion (p=0.015). More importantly, patients with a higher HOTAIR expression showed significantly poorer overall survival than those with lower HOTAIR expression (p<0.05). In conclusion, our results suggest that a high expression of HOTAIR is involved in the progression of cancer and may be a novel biomarker of poor prognosis in patients with EC.

摘要

长链非编码 RNA(lncRNA)正在成为人类癌症中的关键分子。同源盒(HOX)转录反义基因间 RNA(HOTAIR)是一种长链非编码 RNA(lncRNA),与多种人类癌症相关,如乳腺癌、肝癌和肺癌。然而,HOTAIR 是否可以作为子宫内膜癌(EC)的分子标志物尚不清楚。在本研究中,使用定量逆转录 PCR 测定了 66 例 EC 组织和 30 例来自健康年龄匹配对照的正常组织中的 HOTAIR 表达。此外,通过原位杂交,我们测量了 129 例福尔马林固定石蜡包埋(FFPE)组织切片中的 HOTAIR 表达,其中包括 96 例与冷冻病例匹配的组织、21 例其他 EC 组织和 12 例非典型增生组织。分析了 HOTAIR 表达与患者临床病理特征之间的相关性。我们的结果表明,EC 组织中的 HOTAIR 表达明显高于正常组织(p<0.001)。此外,我们观察到 HOTAIR 表达与 EC 分级(p<0.05)和淋巴结转移(p<0.05)之间存在显著相关性。此外,在 FFPE 组织中,但不是在冷冻组织中,我们发现较高的 HOTAIR 表达也与肌层浸润深度(p=0.019)和血管淋巴管侵犯(p=0.015)相关。更重要的是,HOTAIR 表达较高的患者总生存明显差于 HOTAIR 表达较低的患者(p<0.05)。综上所述,我们的研究结果表明,HOTAIR 的高表达参与了癌症的进展,可能是 EC 患者预后不良的新的生物标志物。

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