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长链非编码RNA的差异表达谱揭示了用于鉴定人类胃癌的潜在生物标志物。

Differential expression profiles of long non-coding RNAs reveal potential biomarkers for identification of human gastric cancer.

作者信息

Li Chengyun, Liang Geyu, Yao Wenzhuo, Sui Jing, Shen Xian, Zhang Yanqiu, Ma Shumei, Ye Yancheng, Zhang Zhiyi, Zhang Wenhua, Yin Lihong, Pu Yuepu

机构信息

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, P.R. China.

Gansu Wuwei Tumor Hospital, Wuwei, Gansu 733000, P.R. China.

出版信息

Oncol Rep. 2016 Mar;35(3):1529-40. doi: 10.3892/or.2015.4531. Epub 2015 Dec 29.

Abstract

Gastric cancer (GC) is one of the most lethal malignancies worldwide. To reduce its high mortality, sensitive and specific biomarkers for early detection are urgently needed. Recent studies have reported that tumor-specific long non-coding RNAs (lncRNAs) seem to be potential biomarkers for the early diagnosis and treatment of cancer. In the present study, lncRNA and mRNA expression profiling of GC specimens and their paired adjacent non-cancerous tissues was performed. Differentially expressed lncRNAs and mRNAs were identified through microarray analysis. The function of differential mRNA was determined by gene ontology and pathway analysis and the functions of lncRNAs were studied by constructing a co-expression network to find the relationships with corresponding mRNAs. We connected the co-expression network, mRNA functions, and the results of the microarray profile differential expression and selected 14 significantly differentially expressed key lncRNAs and 21 key mRNAs. Quantitative RT-PCR (qRT-PCR) was conducted to verify these key RNAs in 50 newly diagnosed GC patients. The data showed that RP5-919F19, CTD-2541M15 and UCA1 was significantly higher expressed. AP000459, LOC101928316, RP11-167N4 and LINC01071 expression was significantly lower in 30 advanced GC tumor tissues than adjacent non-tumor tissues P<0.05. Then, we further validated the above significant differential expression candidate lncRNAs in 20 early stage GC patients. Results showed that CTD-2541M15 and UCA1 were significantly higher expressed, AP000459, LINC01071 and MEG3 expression was significantly lower in 20 early stage GC patient tumor tissues than adjacent non-tumor tissues (P<0.05). In addition, expression of these lncRNAs shows gradual upward trend from early stage GC to advanced GC. Furthermore, conditional logistic regression analysis revealed the aberrant expression of CTD-2541M15, UCA1 and MEG3 closely linked with GC. There is a set of differentially expressed lncRNAs in GC which may be associated with the progression and development of GC. The differential expression profiles of lncRNAs in GC may be promising biomarkers for the early detection and early screening of high‑risk populations.

摘要

胃癌(GC)是全球最致命的恶性肿瘤之一。为降低其高死亡率,迫切需要用于早期检测的敏感且特异的生物标志物。最近的研究报道,肿瘤特异性长链非编码RNA(lncRNA)似乎是癌症早期诊断和治疗的潜在生物标志物。在本研究中,对GC标本及其配对的相邻非癌组织进行了lncRNA和mRNA表达谱分析。通过微阵列分析鉴定差异表达的lncRNA和mRNA。通过基因本体论和通路分析确定差异mRNA的功能,并通过构建共表达网络来研究lncRNA的功能,以找到与相应mRNA的关系。我们将共表达网络、mRNA功能以及微阵列谱差异表达结果联系起来,选择了14个显著差异表达的关键lncRNA和21个关键mRNA。对50例新诊断的GC患者进行定量逆转录聚合酶链反应(qRT-PCR)以验证这些关键RNA。数据显示,RP5-919F19、CTD-2541M15和UCA1表达显著升高。在30例晚期GC肿瘤组织中,AP000459、LOC101928316、RP11-167N4和LINC01071的表达显著低于相邻非肿瘤组织(P<0.05)。然后,我们在20例早期GC患者中进一步验证上述显著差异表达的候选lncRNA。结果显示,在20例早期GC患者肿瘤组织中,CTD-2541M15和UCA1表达显著升高,AP000459、LINC01071和MEG3表达显著低于相邻非肿瘤组织(P<0.05)。此外,这些lncRNA的表达从早期GC到晚期GC呈逐渐上升趋势。此外,条件逻辑回归分析显示CTD-2541M15、UCA1和MEG3的异常表达与GC密切相关。GC中存在一组差异表达的lncRNA,可能与GC的进展和发展有关。GC中lncRNA的差异表达谱可能是早期检测和高危人群早期筛查的有前景的生物标志物。

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