切换至 "中华医学电子期刊资源库"
高级检索
中华乳腺病杂志(电子版)

中华乳腺病杂志(电子版) ›› 2015, Vol. 09 ›› Issue (04) : 242 -246. doi: 10.3877/cma. j. issn.1674-0807.2015.04.004

论著

长链非编码RNA 在乳腺癌患者外周血与癌组织中的表达
吕明明1, 许楠1,2, 王凤良1, 陈飞1, 陆迅3, 陆澄1,2,†()   
  1. 1.210004 南京医科大学附属南京市妇幼保健院乳腺病科
    2.210046 南京中医药大学第一临床医学院
    3.210005 南京金陵中学
  • 收稿日期:2015-01-22 出版日期:2015-08-01
  • 通信作者: 陆澄
  • 基金资助:
    国家自然科学基金资助项目(81172501)南京市医学科技发展项目(YKK12103)

Expression of long non-coding RNA in peripheral blood and carcinoma tissue of breast cancer patients

Mingming Lyu1, Nan Xu1,2, Fengliang Wang1, Fei Chen1, Xun Lu3, Cheng Lu1,2,†()   

  1. 1.Department of Breast Surgery, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210004, China
    2.First Clinical Medicine College, Nanjing University of Chinese Medicine, Nanjing 210046,China
    3.Jinling High School, Nanjing 210005, China
  • Received:2015-01-22 Published:2015-08-01
  • Corresponding author: Cheng Lu
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

吕明明, 许楠, 王凤良, 陈飞, 陆迅, 陆澄. 长链非编码RNA 在乳腺癌患者外周血与癌组织中的表达[J/OL]. 中华乳腺病杂志(电子版), 2015, 09(04): 242-246.

Mingming Lyu, Nan Xu, Fengliang Wang, Fei Chen, Xun Lu, Cheng Lu. Expression of long non-coding RNA in peripheral blood and carcinoma tissue of breast cancer patients[J/OL]. Chinese Journal of Breast Disease(Electronic Edition), 2015, 09(04): 242-246.

目的

比较分析长链非编码RNA(lncRNA)在乳腺癌组织与外周血中的表达情况,筛选出参与乳腺癌发生、复发及转移过程中重要的lncRNA。

方法

利用芯片技术分别检测并筛选乳腺癌组织与外周血差异表达的lncRNA 及mRNA,应用生物信息学方法,包括基因本体论(gene ontology, GO)和Pathway 分析, 分析乳腺癌组织与外周血中lncRNA 及mRNA 的表达谱。 分析得到乳腺癌外周血与癌组织中共同表达与特异表达的lncRNA,并且进一步分析差异基因可能调控的相关通路,进而发现参与乳腺癌发生发展和转移过程的lncRNAs。

结果

笔者发现在乳腺癌组织和外周血中共同上调的lncRNA有7 条(包括RP11-707G14.7、RP11-771K4.1、XLOC_013658、RP11-201A3.1、RP11-298H24.1、BM151951、XLOC_011403),共同下调的lncRNA 有12 条(LOC100506035、PWRN1、MAGI2-AS3、RP11-67L3.2、CTC-454M9.1、AC017006.2、AC002456.2、RP11-430B1.2、RP11-945C19.4、RP11-839D17.3、 CTA-407F11.8、LINC00420)。 GO 和Pathway 分析结果表明在乳腺癌患者外周血和组织中均差异表达的基因主要参与调控免疫反应与TGF-β 通路等。

结论

lncRNA 在乳腺癌组织和外周血中呈差异表达,可能参与到乳腺癌的发生、发展以及复发转移中,有可能成为临床诊断与治疗乳腺癌的新靶点。

关键词: 乳腺肿瘤, 分子诊断技术, 芯片分析技术, 基因表达谱, 微RNAs

Objective

To compare the expression of long non-coding RNA (lncRNA) in both peripheral blood and carcinoma tissues of breast cancer patients and reveal the important lncRNAs that may participating in the development, recurrence and metastasis of breast cancer.

Methods

Microarray chip was used to detect and screen the differentially expressed lncRNA and mRNA in carcinoma tissue and peripheral blood of breast cancer patients. lncRNA and mRNA expression profiles were analyzed by bioinformatics tools,including gene ontology (GO) and Pathway analysis. The differentially expressed and commonly expressed lncRNAs both in peripheral blood and carcinoma tissues were detected. Moreover, we further analyzed the relevant pathways regulated by differentially expressed genes, as well as lncRNAs participating in the development and metastasis of breast cancer.

Results

There were 7 up-regulated lncRNAs (including RP11-707G14.7,RP11-771K4.1,XLOC_013658,RP11-201A3.1,RP11-298H24.1,BM151951,XLOC_011403) and 12 down-regulated lncRNAs in both carcinoma tissue and peripheral blood (including LOC100506035,PWRN1, MAGI2-AS3, RP11-67L3.2, CTC-454M9.1,AC017006.2, AC002456.2, RP11-430B1.2, RP11-945C19.4, RP11-839D17.3, CTA-407F11.8, LINC00420). GO and Pathway analysis indicated that differentially expressed genes in both peripheral blood and carcinoma tissues of breast cancer patients were mainly involved in the regulation of immune response and TGF-β pathway.

Conclusion

lncRNAs were differentially expressed genes in both peripheral blood and carcinoma tissues of breast cancer patients, which may be involved in the development, recurrence and metastasis of breast cancer, regarded as possible potential targets for clinical diagnosis and treatment.

Key words: Breast neoplasms, Molecular diagnostic techniques, Microchip analytical procedures, Gene expression profiling, MicroRNAs
表1 乳腺癌组织与外周血中共同上调的长链非编码RNA
序列名 长链非编码RNA RNA长度(nt) 染色体部位 正/反义链(+/-) 序列起始位点 序列结束位点
ENST00000535936 RP11-707G14.7 383 chr11 + 73639577 73641417
ENST00000541749 RP11-771K4.1 868 chr12 - 31516414 31522235
TCONS_00028623 XLOC_013658 652 chr20 - 12915531 12916654
ENST00000569873 RP11-201A3.1 2 277 chr1 + 188187530 188189807
ENST00000424701 RP11-298H24.1 551 chr10 + 107900048 107917903
BM151951 BM151951 330 chr3 + 72792571 72792897
TCONS_00024045 XLOC_011403 211 chr15 - 24587892 24588655
表2 乳腺癌组织与外周血中共同下调的长链非编码RNA
序列名 长链非编码RNA RNA长度(nt) 染色体部位 正/反义链(+/-) 序列起始位点 序列结束位点
NR_038826 LOC100506035 2 054 chr4 + 80413746 80497614
ENST00000569908 PWRN1 1 435 chr15 + 24803304 24804739
NR_038346 MAGI2-AS3 901 chr7 + 79082272 79100524
ENST00000450503 RP11-67L3.2 343 chr1 + 55258557 55260578
ENST00000514571 CTC-454M9.1 594 chr5 + 88261691 88464485
ENST00000444077 AC017006.2 464 chr2 - 46305153 46305967
ENST00000412669 AC002456.2 449 chr7 - 90219936 90226667
ENST00000560518 RP11-430B1.2 1 972 chr15 + 52472413 52498071
ENST00000582939 RP11-945C19.4 620 chr18 + 5887485 5889462
ENST00000533504 RP11-839D17.3 517 chr11 - 113150104 113185159
ENST00000453811 CTA-407F11.8 451 chr22 - 25959067 25960226
ENST00000443554 LINC00420 1 059 chr13 - 19982181 19983669
图1 乳腺癌差异基因GO 分析 注:a 图所示上调基因参与的生物学过程分析;b 图所示上调基因涉及细胞组分分析;c 图所示上调基因参与的分子功能分析;d 图所示下调基因参与的生物学过程分析;e 图所示下调基因涉及细胞组分分析;f 图所示下调基因参与的分子功能分析
图2 乳腺癌差异基因Pathway 分析
[1]
Ferlay J, Shin HR, Bray F, et al. Cancer incidence and mortality worldwide: IARC Cancer Base No. 10. GLOBOCAN 2008 [M]. Lyon: International Agency for Research on Cancer,2010.
[2]
Fan L, Strasser-Weippl K, Li JJ,et al. Breast cancer in China[J]. Lancet Oncol,2014,15(7):e279-289.
[3]
Dos Anjos Pultz B,da Luz FA,de Faria PR,et al. Far beyond the usual biomarkers in breast cancer: a review[J]. J Cancer,2014,5(7):559-571.
[4]
ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome[J]. Nature, 2012, 489(7414),57-74.
[5]
Tang J, Ahmad A, Sarkar FH. The role of microRNAs in breast cancer migration, invasion and metastasis[J]. Int J Mol Sci,2012,13(10):13414-13437.
[6]
BergamaschiA,KatzenellenbogenBS.Tamoxifen downregulation of miR-451 increases 14-3-3ζ and promotes breast cancer cell survival and endocrine resistance [J].Oncogene,2012,31(1):39-47.
[7]
Spizzo R, Almeida MI, Colombatti A, et al. Long non-coding RNAs and cancer: a new frontier of translational research?[J]. Oncogene,2012,31(43):4577-4587.
[8]
Gupta RA, Shah N, Wang KC, et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis[J]. Nature,2010,464(7291):1071-1076.
[9]
高纪东,王军,张保宁,等. 乳腺癌外周血微转移与远处转移的相关性[J]. 癌症,2007,26(12):1385-1387.
[10]
Xu N, Wang F, Lv M, et al. Microarray expression profile analysis of long non-coding RNAs in human breast cancer: a study of Chinese women[J]. Biomed Pharmacother,2015,69:221-227.
[11]
Gene Ontology Consortium. The Gene Ontology (GO) project in 2006[J]. Nucleic Acids Res,2006,34(Database issue):D322-326.
[12]
Curtis RK,Oresic M,Vidal-Puig A. Pathways to the analysis of microarrays data[J]. Trends Biotechnol, 2005, 23(8):429-435.
[13]
Dong C, Chen L. Second malignancies after breast cancer: the impact of adjuvant therapy[J]. Mol Clin Oncol,2014,2(3):331-336.
[14]
Kalia M. Biomarkers for personalized oncology:recent advances and future challenges[J]. Metabolism,2015,64(3 Suppl 1):S16-21.
[15]
Ye S, Yang L,Zhao X,et al. Bioinformatics method to predict two regulation mechanism: TF-miRNA-mRNA and lncRNAmiRNA-mRNA in pancreatic cancer [ J]. Cell Biochem Biophys,2014,70(3):1849-1858.
[16]
Xue Y, Ma G, Gu D, et al. Genome-wide analysis of long noncoding RNA signature in human colorectal cancer[J].Gene,2015,556(2):227-234.
[17]
Prensner JR, Chen W, Han S, et al. The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc[J]. Neoplasia,2014,16(11):900-908.
[18]
Peng W, Gao W, Feng J. Long noncoding RNA HULC is a novel biomarker of poor prognosis in patients with pancreatic cancer[J]. Med Oncol,2014,31(12):346.
[19]
Principe DR, Doll JA, Bauer J, et al. TGF-β: duality of function between tumor prevention and carcinogenesis [J]. J Natl Cancer Inst,2014,106(2):djt369.
[1] 李洋, 蔡金玉, 党晓智, 常婉英, 巨艳, 高毅, 宋宏萍. 基于深度学习的乳腺超声应变弹性图像生成模型的应用研究[J/OL]. 中华医学超声杂志（电子版）, 2024, 21(06): 563-570.
[2] 河北省抗癌协会乳腺癌专业委员会护理协作组. 乳腺癌中心静脉通路护理管理专家共识[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 321-329.
[3] 刘晨鹭, 刘洁, 张帆, 严彩英, 陈倩, 陈双庆. 增强MRI 影像组学特征生境分析在预测乳腺癌HER-2 表达状态中的应用[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 339-345.
[4] 张晓宇, 殷雨来, 张银旭. 阿帕替尼联合新辅助化疗对三阴性乳腺癌的疗效及预后分析[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 346-352.
[5] 邱琳, 刘锦辉, 组木热提·吐尔洪, 马悦心, 冷晓玲. 超声影像组学对致密型乳腺背景中非肿块型乳腺癌的诊断价值[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 353-360.
[6] 程燕妮, 樊菁, 肖瑶, 舒瑞, 明昊, 党晓智, 宋宏萍. 乳腺组织定位标记夹的应用与进展[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 361-365.
[7] 涂盛楠, 胡芬, 张娟, 蔡海峰, 杨俊泉. 天然植物提取物在乳腺癌治疗中的应用[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 366-370.
[8] 朱文婷, 顾鹏, 孙星. 非酒精性脂肪性肝病对乳腺癌发生发展及治疗的影响[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 371-375.
[9] 周荷妹, 金杰, 叶建东, 夏之一, 王进进, 丁宁. 罕见成人肋骨郎格汉斯细胞组织细胞增生症被误诊为乳腺癌术后骨转移一例[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(06): 380-383.
[10] 葛睿, 陈飞, 李杰, 李娟娟, 陈涵. 多基因检测在早期乳腺癌辅助治疗中的应用价值[J/OL]. 中华乳腺病杂志(电子版), 2024, 18(05): 257-263.
[11] 高杰红, 黎平平, 齐婧, 代引海. ETFA和CD34在乳腺癌中的表达及与临床病理参数和预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 64-67.
[12] 韩萌萌, 冯雪园, 马宁. 乳腺癌改良根治术后桡神经损伤1例[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 117-118.
[13] 张志兆, 王睿, 郜苹苹, 王成方, 王成, 齐晓伟. DNMT3B与乳腺癌预后的关系及其生物学机制[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 624-629.
[14] 王玲艳, 高春晖, 冯雪园, 崔鑫淼, 刘欢, 赵文明, 张金库. 循环肿瘤细胞在乳腺癌新辅助及术后辅助治疗中的应用[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 630-633.
[15] 赵林娟, 吕婕, 王文胜, 马德茂, 侯涛. 超声引导下染色剂标记切缘的梭柱型和圆柱型保乳区段切除术的效果研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 634-637.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号