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结直肠癌中长链非编码 RNA:一项计算机分析研究

Long Noncoding RNAs in Colorectal Adenocarcinoma; an in silico Analysis.

机构信息

Department of Biotechnology, Ahvaz Branch, Islamic Azad University, Ahvaz, Iran.

Department of Molecular Genetics, Faculty of Biosciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Pathol Oncol Res. 2019 Oct;25(4):1387-1394. doi: 10.1007/s12253-018-0428-2. Epub 2018 Jun 13.

Abstract

Long noncoding RNAs (lncRNAs) are lengthy noncoding transcripts which are involved in critical signaling pathways including cell cycle and apoptosis so it is not surprising to see their altered expression in human tumors. Colorectal adenocarcinoma is one the most frequent malignancies worldwide. The role of lncRNAs in colorectal adenocarcinoma is not well understood. To study the significance of lncRNAs in colorectal adenocarcinoma, we retrieved 189 approved lncRNAs from HGNC. The genes were imported into the cBioPortal database for transcriptomic analyses. We queried all the samples from TCGA provisional colorectal adenocarcinoma with RNA-seq v2 data in our study and considered RNA dysregulation with Z-score: ±2. The lncRNA which was altered in most of the patients were considered as "significant lncRNA" for further analyses. We considered the association of candidate lncRNAs with clinicopathologic parameters of samples including tumor disease anatomic site, neoplasm histologic types, tumor stage and survival. We also compute the specificity of the significant lncRNAs expression in colorectal adenocarcinoma comparing with other human cancers in cancer portal. Our analysis showed that lncRNAs SNHG6, PVT1 and ZFAS1 allocated the maximum alteration among the colorectal cases. The expression of SNHG6 and ZFAS1 was more in rectal adenocarcinoma than the colon carcinoma while the PVT1 showed the same expression levels in both tissues. However, we found that upregulation of PVT1 has been reduced the overall survival in patients. Altogether these data showed SNHG6, PVT1 and ZFAS1, are promising candidates for experimental research on colorectal adenocarcinoma to discover novel biomarker for this prevalent cancer.

摘要

长链非编码 RNA(lncRNA)是长度较长的非编码转录物,参与包括细胞周期和细胞凋亡在内的关键信号通路,因此在人类肿瘤中看到它们的表达改变并不奇怪。结直肠腺癌是全球最常见的恶性肿瘤之一。lncRNAs 在结直肠腺癌中的作用尚未得到充分理解。为了研究 lncRNAs 在结直肠腺癌中的意义,我们从 HGNC 中检索了 189 个已批准的 lncRNA。将这些基因导入 cBioPortal 数据库进行转录组分析。我们在研究中查询了 TCGA 临时结直肠腺癌所有具有 RNA-seq v2 数据的样本,并考虑使用 Z 分数:±2 来衡量 RNA 失调。在大多数患者中发生改变的 lncRNA 被认为是进一步分析的“显著 lncRNA”。我们考虑了候选 lncRNAs 与样本临床病理参数的关联,包括肿瘤疾病解剖部位、肿瘤组织学类型、肿瘤分期和生存情况。我们还在癌症门户中比较了显著 lncRNAs 在结直肠腺癌中的表达特异性与其他人类癌症。我们的分析表明,lncRNAs SNHG6、PVT1 和 ZFAS1 在结直肠病例中分配的改变最大。SNHG6 和 ZFAS1 的表达在直肠腺癌中高于结肠癌,而 PVT1 在两种组织中的表达水平相同。然而,我们发现 PVT1 的上调降低了患者的总生存率。总的来说,这些数据表明 SNHG6、PVT1 和 ZFAS1 是结直肠腺癌实验研究的有前途的候选者,可以为这种常见癌症发现新的生物标志物。

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