基因间长链非编码RNA RP11-488L18.10在胆管癌中的表达及其与预后的关系

谭峥嵘; 丰大利; 张清

doi:10.3969/j.issn.1001-5256.2020.05.027

基因间长链非编码RNA RP11-488L18.10在胆管癌中的表达及其与预后的关系

DOI: 10.3969/j.issn.1001-5256.2020.05.027

1. 宜昌市第二人民医院三峡大学第二人民医院消化内科
2. 宜昌市第二人民医院三峡大学第二人民医院肿瘤科

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中图分类号: R735.8
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- 出版日期: 2020-05-20

Expression of intergenic long non-coding RNA RP11-488L18.10 in cholangiocarcinoma and its association with prognosis

Department of Gastroenterology, The Second People’s Hospital of Yichang & The Second People’s Hospital of China Three Gorges University, Yichang, Hubei 443000, China

摘要

摘要:
目的筛选胆管癌（CCA）中关键基因间长链非编码RNA（lincRNA）,并研究其表达与患者预后的关系。方法 CCA表达量和临床数据来自于人类癌症基因组图谱（TCGA）。数据集GSE107943 CCA表达数据获取自高通量基因表达数据库（GEO）。利用R软件进行差异性基因分析,确定肿瘤和正常样品之间显著差异性表达的lincRNA;筛选关键lincRNA。使用受试者工作特征曲线（ROC曲线）分析基因表达对CCA的诊断意义。使用Kaplan-Meier生存曲线分析患者预后。基因富集分析分析显著富集分通路。实时荧光定量PCR验证临床样本中基因表达。结果通过筛选得到451个同时在TCGA和GSE107943数据集上调的lincRNA和154个同时两个数据集下调的lincRNA。在TCGA和GSE107943数据集中lincRNA RP11-488L18. 10在肿瘤组织中丰度较高。利用TCGA和GSE107943数据集对lincRNA RP11-488L18. 10的表达与CCA的关系进行ROC曲线分析,结果显示,TCGA中AUC=1,P<0. 000 1;在GSE107943中AUC=0...
- 胆管肿瘤 /
- RNA,长链非编码 /
- 预后
Abstract:
Objective To screen out the key intergenic long non-coding RNAs(lncRNAs) in cholangiocarcinoma(CCA) and their association with patient prognosis.Methods CCA expression and clinical data were obtained from The Cancer Genome Atlas(TCGA). High-throughput gene expression data in GSE107943 dataset were obtained from the Gene Expression Omnibus(GEO). R software was used to analyze differentially expressed genes and determine significantly differentially expressed lncRNAs between tumor and normal samples, and the key lncRNAs were screened out. The receiver operating characteristic(ROC) curve was used to analyze the value of gene expression in the diagnosis of CCA; the Kaplan-Meier survival curves were used to analyze prognosis; Gene Set Enrichment Analysis(GSEA) was used to investigate significantly enriched pathways; quantitative real-time PCR was used to verify gene expression in clinical samples.Results A total of 451 upregulated lncRNAs and 154 downregulated lncRNAs in both TCGA and GSE107943 dataset were screened out. The lncRNA RP11-488 L18.10 in TCGA and GSE107943 dataset was highly abundant in tumor tissue. Based on TCGA and GSE107943 dataset, the ROC curve analysis of the association between lncRNA RP11-488 L18.10 expression and CCA showed that the expression of lncRNA RP11-488 L18.10 had an area under the ROC curve of 1 in TCGA(P< 0. 000 1) and 0. 9469 in GSE107943(P< 0. 000 1). In TCGA, the high expression of lncRNA RP11-488 L18.10 significantly predicted overall survival rate(P= 0. 016) and recurrence-free survival rate(P= 0. 017) in patients with CCA; in GSE107943, the high expression of lncRNA RP11-488 L18. 10 significantly predicted overall survival rate(P= 0. 023) and recurrence-free survival rate(P= 0. 005) in patients with CCA. LncRNA RP11-488 L18. 10 was significantly positively correlated with MCM2. Compared with the adjacent tissue, CCA tissue had high expression of lncRNA RP11-488 L18.10(P= 0.010) and MCM2(P= 0. 023).Conclusion LncRNA RP11-488 L18. 10 is closely associated with the development and prognosis of CCA and thus may become a target for the diagnosis and treatment of CCA.
- bile duct neoplasms /
- RNA,long untranslated /
- prognosis

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参考文献(22)

[1] RAZUMILAVA N, GORES GJ. Cholangiocarcinoma[J]. Lancet, 2014, 383(9935):2168-2179.

[2] YAN X, HU Z, FENG Y, et al. Comprehensive genomic characterization of long non-coding RNAs across human cancers[J]. Cancer Cell, 2015, 28(4):529-540.

[3] XU H, ZHOU M, CAO Y, et al. Genome-wide analysis of long noncoding RNAs, microRNAs, and mRNAs forming a competing endogenous RNA network in repeated implantation failure[J]. Gene, 2019, 720:144056.

[4] RANSOHOFF JD, WEI Y, KHAVARI PA. The functions and unique features of long intergenic non-coding RNA[J]. Nat Rev Mol Cell Biol, 2018, 19(3):143-157.

[5] QUINN JJ, CHANG HY. Unique features of long non-coding RNA biogenesis and function[J]. Nat Rev Genet, 2016, 17(1):47-62.

[6] DENIZ E, ERMAN B. Long noncoding RNA(lincRNA), a new paradigm in gene expression control[J]. Funct Integr Genomics, 2017, 17(2-3):135-143.

[7] AHN KS, KANG KJ, KIM YH, et al. Genetic features associated with(18)F-FDG uptake in intrahepatic cholangiocarcinoma[J]. Ann Surg Treat Res, 2019, 96(4):153-161.

[8] SUBRAMANIAN A, TAMAYO P, MOOTHA VK, et al. Gene set enrichment analysis:A knowledge-based approach for interpreting genome-wide expression profiles[J]. Proc Natl Acad Sci U S A, 2005, 102(43):15545-15550.

[9] CHEN XP, XIANG S. Therapy of hilar cholangiocarcinoma in the precise medicine period[J]. Chin J Surg, 2018, 17(1):3-8.(in Chinese）陈孝平，项帅．精准医学时代肝门部胆管癌的治疗[J]．中华消化外科杂志，2018, 17(1):3-8.

[10] CABILI MN, TRAPNELL C, GOFF L, et al. Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses[J]. Genes Dev, 2011, 25(18):1915-1927.

[11] IYER MK, NIKNAFS YS, MALIK R, et al. The landscape of long noncoding RNAs in the human transcriptome[J]. Nat Genet, 2015, 47(3):199-208.

[12] WINKLE M, KLUIVER JL, DIEPSTRA A, et al. Emerging roles for long noncoding RNAs in B-cell development and malignancy[J]. Crit Rev Oncol Hematol, 2017, 120:77-85.

[13] GOYAL N, KESHARWANI D, DATTA M. Lnc-ing non-coding RNAs with metabolism and diabetes:Roles of lncRNAs[J]. Cell Mol Life Sci, 2018, 75(10):1827-1837.

[14] ZHANG B, GUNAWARDANE L, NIAZI F, et al. A novel RNA motif mediates the strict nuclear localization of a long noncoding RNA[J]. Mol Cell Biol, 2014, 34(12):2318-2329.

[15] YIN HZ, GUO HL, PEI Y, et al. Research progress of long noncoding RNA in primary liver cancer[J]. China Med Herald,2019, 16(20):34-37.(in Chinese）殷宏振，郭化磊，裴颖，等．长链非编码RNA在原发性肝癌中的研究进展[J]．中国医药导报，2019, 16(20):34-37.

[16] CAI Y, YAN P, ZHANG G, et al. Long non-coding RNA TP73-AS1 sponges miR-194 to promote colorectal cancer cell proliferation, migration and invasion via up-regulating TGFalpha[J]. Cancer Biomark, 2018, 23(1):145-156.

[17] LU XW, XU N, ZHENG YG, et al. Increased expression of long noncoding RNA LINC00961 suppresses glioma metastasis and correlates with favorable prognosis[J]. Eur Rev Med Pharmacol Sci, 2018, 22(15):4917-4924.

[18] ZHANG J, JU C, ZHANG W, et al. LncRNA SNHG20 is associated with clinical progression and enhances cell migration and invasion in osteosarcoma[J]. IUBMB Life, 2018, 70(11):1115-1121.

[19] TANG L, WANG Y, WANG H, et al. Long noncoding-RNA component of mitochondrial RNA processing endoribonuclease is involved in the progression of cholangiocarcinoma by regulating microRNA-217[J]. Cancer Sci, 2019, 110(7):2166-2179.

[20] LI Y, CAI Q, LI W, et al. Long non-coding RNA EPIC1 promotes cholangiocarcinoma cell growth[J]. Biochem Biophys Res Commun, 2018, 504(4):654-659.

[21] DENG M, SUN J, XIE S, et al. Inhibition of MCM2 enhances the sensitivity of ovarian cancer cell to carboplatin[J]. Mol Med Rep, 2019, 20(3):2258-2266.

[22] TOKES T, TOKES AM, SZENTMARTONI G, et al. Prognostic and clinicopathological correlations of cel cycle marker expressions before and after the primary systemic therapy of breast cancer[J]. Pathol Oncol Res, 2019.[Online ahead of print]

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