结直肠癌中差异性表达的外泌体lncRNA功能富集及通路分析

曾薇; 刘翼; 李文婷; 朱金峰

doi:10.16766/j.cnki.issn.1674-4152.002297

结直肠癌中差异性表达的外泌体lncRNA功能富集及通路分析

doi: 10.16766/j.cnki.issn.1674-4152.002297

曾薇^{1, 2},
刘翼³,
李文婷⁴,
朱金峰^{5, 6, ,}

1.
新疆医科大学附属肿瘤医院肺内科，新疆乌鲁木齐 830011
2.
深圳大学总医院血液肿瘤科，广东深圳 518055
3.
深圳大学总医院胸心外科，广东深圳 518055
4.
深圳大学总医院病理科，广东深圳 518055
5.
新疆医科大学附属肿瘤医院胃肠外科，新疆乌鲁木齐 830011
6.
深圳大学总医院普外科，广东深圳 518055

基金项目:

新疆维吾尔自治区自然科学基金面上项目 2018D01C255

详细信息

通讯作者:
朱金峰，E-mail：zjf122@hotmail.com

中图分类号: R735.3 R34
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- 被引次数: 0
出版历程
- 收稿日期: 2021-02-03
- 网络出版日期: 2022-03-03

Functional enrichment and pathway analysis of differential expression of exosome lncRNA in colorectal cancer

ZENG Wei^{1, 2},
LIU Yi³,
LI Wen-ting⁴,
ZHU Jin-feng^{5, 6
, ,}

1.
First Department of Lung Cancer Chemotherapy, the Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830011, China

摘要

摘要: 目的通过探讨差异性表达的外泌体lncRNA及其调控的信号通路在结直肠癌发生、发展中的作用，以期为结直肠癌的诊断和治疗提供新的靶点。方法使用R软件线性回归模型软件包limma包进行差异表达分析，根据筛选阈值得到显著差异表达的lncRNA和mRNA；通过计算差异表达lncRNA与mRNA皮尔逊相关性系数，获得其之间协同表达关系，通过相关系数筛选存在正向协同表达的lncRNA-mRNA关系对；分别对lncRNA的协同表达mRNA进行GO功能和KEGG通路富集分析，以间接预测lncRNA的功能。结果在32例健康志愿者和12例结直肠癌患者中筛选出差异性表达的外泌体lncRNA共202个、mRNA共1 014个。验证出差异性表达的lncRNA-mRNA关系对10个。对lncRNA协同表达的mRNA进行功能富集显示，差异性表达的外泌体lncRNA可能与B细胞受体信号通路、NF-κB信号通路、JAK-STAT信号通路、抗原处理与呈递信号通路和NOD样受体信号通路活化密切相关。结论深入探索外泌体lncRNA在结直肠癌中的差异性表达、功能富集及通路活化，有助于为结直肠癌的治疗提供新思路，为诊断提供新靶点。
- 结直肠癌 /
- 外泌体 /
- 长链非编码RNA
Abstract: Objective To explore the role of differential expression of exosome lncRNA and its regulated signal pathway in the occurrence and development of colorectal cancer and provide a new target for the diagnosis and treatment of colorectal cancer. Methods The linear regression model package limma of R software was used to analyse the differential expression of lncRNA and mRNA. By calculating the Pearson correlation coefficient between differentially expressed lncRNA and mRNA, their co-expression was obtained. The positive co-expression of lncRNA-mRNA was screened by using a correlation coefficient. Go function and KEGG pathway enrichment of mRNA co-expressed with lncRNA were analysed to indirectly predict the function of lncRNA. Results A total of 202 differentially expressed exosome lncRNAs and 1014 exosome mRNA were screened from 32 healthy volunteers and 12 colorectal cancer patients. Ten pairs of lncRNA-mRNA co-expression were verified. Functional enrichment of mRNA co-expressed by lncRNA showed that differentially expressed exosome lncRNA may be closely related to B cell receptor signal pathway, NF-KB signal pathway, JAK-STAT signal pathway, antigen processing and presentation signal pathway and NOD-like receptor signal pathway activation. Conclusion In-depth exploration of differential expression, functional enrichment and pathway activation of exosome lncRNA in colorectal cancer is important to provide new ideas for the diagnosis and treatment of colorectal cancer.
- Colorectal cancer /
- Exosome /
- Long non-coding RNA

HTML全文

图 1 lncRNA协同表达mRNA KEGG通路富集分析结果

注：GeneRatio指该lncRNA靶基因中位于KEGG条目的基因数目与该组基因在KEGG数据库中有注释的基因数目(横坐标下面的数值)，横坐标为lncRNA，纵坐标为富集条目名称。

下载: 全尺寸图片幻灯片

表 1 结直肠癌外泌体中差异表达lncRNA、mRNA统计信息

差异表达的RNA	上调	下调	合计	阈值
lncRNA	112	90	202	\|log₂FC\|>1.000，P < 0.05
mRNA	436	578	1 014	\|log₂FC\|>0.585，P < 0.05

下载: 导出CSV

参考文献(20)

[1]	GRAF W D. Exome Sequencing and molecular diagnosis[J]. Dtsch Arztebl Int, 2019, 116(12): 195-196. http://www.ncbi.nlm.nih.gov/pubmed/31056084
[2]	MENG W, HAO Y, HE C, et al. Exosome-orchestrated hypoxic tumor microenvironment[J]. Mol Cancer, 2019, 18(1): 57. doi: 10.1186/s12943-019-0982-6
[3]	PENG W X, KOIRALA P, MO Y Y. LncRNA-mediated regulation of cell signaling in cancer[J]. Oncogene, 2017, 36(41): 5661-5667. doi: 10.1038/onc.2017.184
[4]	GHAFOURI-FARD S, ESMAEILI M, TAHERI M. H19 lncRNA: Roles in tumorigenesis[J]. Biomed Pharmacother, 2020, 123: 109774. DOI: 10.1016/j.biopha.2019.109774.
[5]	曾薇, 刘翼, 李文婷, 等. lncRNA DLEU2转录调控因子的生物信息学分析[J]. 中华全科医学, 2021, 19(7): 1114-1116, 1120. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY202107012.htm
[6]	SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660
[7]	CHEN W, ZHENG R, BAADE P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. doi: 10.3322/caac.21338
[8]	张卫刚, 张言言, 张宪文, 等. 不同分期结直肠癌患者的预后分析: 一项基于SEER数据库的回顾性研究[J]. 中华结直肠疾病电子杂志, 2017, 6(1): 21-27. doi: 10.3877/cma.j.issn.2095-3224.2017.01.005
[9]	SEO N, AKIYOSHI K, SHIKU H. Exosome-mediated regulation of tumor immunology[J]. Cancer Sci, 2018, 109(10): 2998-3004. doi: 10.1111/cas.13735
[10]	WU Q, ZHOU L, LV D, et al. Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression[J]. J Hematol Oncol, 2019, 12(1): 53. doi: 10.1186/s13045-019-0739-0
[11]	SUN Z, YANG S, ZHOU Q, et al. Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment[J]. Mol Cancer, 2018, 17(1): 82. doi: 10.1186/s12943-018-0831-z
[12]	MASHOURI L, YOUSEFI H, AREF A R, et al. Exosomes: Composition, biogenesis, and mechanisms in cancer metastasis and drug resistance[J]. Mol Cancer, 2019, 18(1): 75. doi: 10.1186/s12943-019-0991-5
[13]	ZHENG R, DU M, WANG X, et al. Exosome-transmitted long non-coding RNA PTENP1 suppresses bladder cancer progression[J]. Mol Cancer, 2018, 17(1): 143. doi: 10.1186/s12943-018-0880-3
[14]	LIANG Y, SONG X, LI Y, et al. LncRNA BCRT1 promotes breast cancer progression by targeting miR-1303/PTBP3 axis[J]. Mol Cancer, 2020, 19(1): 85. doi: 10.1186/s12943-020-01206-5
[15]	JIANG F, LIU M, WANG H, et al. Wu Mei Wan attenuates CAC by regulating gut microbiota and the NF-κB/IL6-STAT3 signaling pathway[J]. Biomed Pharmacother, 2020, 125: 109982. DOI: 10.1016/j.biopha.2020.109982.
[16]	HONG Y G, XIN C, ZHENG H, et al. miR-365a-3p regulates ADAM10-JAK-STAT signaling to suppress the growth and metastasis of colorectal cancer cells[J]. J Cancer, 2020, 11(12): 3634-3644. doi: 10.7150/jca.42731
[17]	GARAUD S, BUISSERET L, SOLINAS C, et al. Tumor infiltrating B-cells signal functional humoral immune responses in breast cancer[J]. JCI Insight, 2019, 5(18): e129641.
[18]	OLDHAM R J, MOCKRIDGE CI, JAMES S, et al. FcγRII (CD32) modulates antibody clearance in NOD SCID mice leading to impaired antibody-mediated tumor cell deletion[J]. J Immunother Cancer, 2020, 8(1): e000619. DOI: 10.1136/jitc-2020-000619.
[19]	MAYKEL J, LIU J H, LI H, et al. NOD-scidIl2rg (tm1Wjl) and NOD-Rag1 (null) Il2rg (tm1Wjl) : A model for stromal cell-tumor cell interaction for human colon cancer[J]. Dig Dis Sci, 2014, 59(6): 1169-1179. doi: 10.1007/s10620-014-3168-5
[20]	WANG S, HE Z, WANG X, et al. Antigen presentation and tumor immunogenicity in cancer immunotherapy response prediction[J]. Elife, 2019, 8: e49020. DOI: 10.7554/eLife.49020.