您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2021, Vol. 59 ›› Issue (7): 74-84.doi: 10.6040/j.issn.1671-7554.0.2021.0002

• • 上一篇    下一篇

利用数据库信息构建乳腺癌免疫关联lncRNAs风险评估模型

李皖皖1,周文凯1,董书晴1,贺士卿1,刘钊2,张家新2,刘斌3   

  • 出版日期:2021-07-10 发布日期:2021-07-16
  • 通讯作者: 刘斌. E-mail:xyfyzlwk@163.com 张家新. E-mail:ZJX321_321@163.com

Construct of a risk assessment model of breast cancer immune-related lncRNAs based on the database information

LI Wanwan1, ZHOU Wenkai1, DONG Shuqing1, HE Shiqing1, LIU Zhao2, ZHANG Jiaxin2, LIU Bin3   

  1. 1.Xuzhou Medical University, Xuzhou 221000, Jiangsu, China;
    2. Department of Thyroid and Breast Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu, China;
    3. Department of Hepatobiliary and Pancreatic Hernia, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221000, Jiangsu, China
  • Online:2021-07-10 Published:2021-07-16

摘要: 目的 筛选乳腺癌中免疫关联长链非编码RNA(lncRNA),并构建乳腺癌预后风险评估模型,探索预后相关因素。 方法 从UCSC Xena(https://xena.ucsc.edu/)、TCGA、immport(https://www.immport.org/home)官网分别下载乳腺癌患者的测序数据、临床信息以及免疫基因集,并将这些数据进行整理和清洗,最终得到乳腺癌免疫关联lncRNA表达矩阵及临床信息。利用单因素Cox和多因素Cox回归分析筛选出与预后相关的免疫关联 lncRNA,用于构建预后风险评分。根据风险评分的中位数,将患者分为高风险组和低风险组,利用Kaplan-Meier(K-M)生存分析、受试者工作特征曲线(ROC)分析及独立预后因素评估对模型进行评价,并将此模型联合其他临床因素构建列线图,对乳腺癌患者进行生存率预测。 结果 最终确定10个免疫关联 lncRNAs 用来构建风险评分模型;高风险组较低风险组预后差;风险评分可作为乳腺癌患者的独立预后因素;列线图的C指数(CI)为0.751,校准图显示预测值与实际观测值一致性较好。 结论 由10个免疫关联lncRNAs 组成的风险评分模型可用于评估乳腺癌患者的预后,由此建立的列线图可进一步预测乳腺癌患者的生存率。

关键词: 乳腺癌, 长链非编码RNA, 免疫, 预后, 预测模型

Abstract: Objective To screen the immune-related long non-coding RNA(lncRNA)in breast cancer, construct a breast cancer prognostic risk assessment model, and explore the prognostic factors. Methods The sequencing data, clinical information and immune gene set of breast cancer patients from the official websites of UCSC Xena(https://xena.ucsc.edu/), TCGA, and immport(https://www.immport.org/home)were downloaded. The data were sorted and cleaned, and finally breast cancer immune-related lncRNA expression matrix and clinical information were got. Univariate Cox regression analysis and Multivariate Cox regression analysis were used to screen out lncRNAs related to prognosis, so as to construct a prognostic risk score. According to the median risk score, the patients were divided into high-risk and low-risk groups. Kaplan-Meier(K-M)survival analysis, receiver operating characteristic(ROC)curve analysis and independent prognostic factor evaluation were used to evaluate the model. Combined with other clinical factors and risk scores of breast cancer, a nomogram was drawn to predict the individual survival rate of breast cancer patients. Results Ten immune-related lncRNAs were determined to construct a risk scoring model. The high-risk group had a poorer prognosis compared with the low-risk group. Risk score could be used as an independent prognostic factor for breast cancer. The C-index(CI)of the nomogram was 0.751. The calibration chart showed that the predicted value was in good agreement with the actual observation value. Conclusion A risk scoring model composed of 10 immune-related lncRNAs can be used to assess the prognosis of the breast cancer patients, and the corresponding nomogram can further predict the survival rate.

Key words: Breast cancer, Long non-coding RNA, Immunity, Prognosis, Predictive model

中图分类号: 

  • R736.3
[1] DeSantis CE, Ma J, Gaudet MM, et al. Breast cancer statistics, 2019[J]. CA Cancer J Clin, 2019, 69(6): 438-451.
[2] Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2018, 68(6): 394-424.
[3] Amelio I, Bernassola F, Candi E. Emerging roles of long non-coding RNAs in breast cancer biology and management [J]. Semin Cancer Biol, 2021, 72: 36-45. doi: 10.1016/j.semcancer.2020.06.019.
[4] Harbeck N, Penault-Llorca F, Cortes J, et al. Breast cancer [J]. Nat Rev Dis Primers, 2019, 5(1): 66. doi: 10.1038/s41572-019-0111-2.
[5] Shen Y, Peng X, Shen C. Identification and validation of immune-related lncRNA prognostic signature for breast cancer [J]. Genomics, 2020, 112(3): 2640-2646.
[6] Saleh R, Elkord E. Acquired resistance to cancer immunotherapy: role of tumor-mediated immunosuppression [J]. Semin Cancer Biol, 2020, 65: 13-27. doi:10.1016/j.semcancer.2019.07.017.
[7] Vishnubalaji R, Shaath H, Elango R, et al. Noncoding RNAs as potential mediators of resistance to cancer immunotherapy [J]. Semin Cancer Biol, 2020, 65: 65-79. doi: 10.1016/j.semcancer.2019.11.006.
[8] 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.
[9] Nagano T, Fraser P. No-nonsense functions for long noncoding RNAs [J]. Cell, 2011, 145(2): 178-181.
[10] Fatica A, Bozzoni I. Long non-coding RNAs: new players in cell differentiation and development [J]. Nat Rev Genet, 2014, 15(1): 7-21.
[11] Han CL, Ge M, Liu YP, et al. Long non-coding RNA H19 contributes to apoptosis of hippocampal neurons by inhibiting let-7b in a rat model of temporal lobe epilepsy [J]. Cell Death Dis, 2018, 9(6): 617. doi: 10.1038/s41419-018-0496-y.
[12] Lin YH, Wu MH, Yeh CT, et al. Long non-coding RNAs as mediator of tumor microenvironment and live cancer cell communication [J]. Int J Mol Sci, 2018, 19(12): 3742. doi: 10.3390/ijms19123742.
[13] Dykes IM, Emanueli C. Transcriptional and post-transcriptional gene regulation by long non-coding RNA [J]. Genomics Proteomics Bioinformatics, 2017, 15(3): 177-186. doi:10.1016/j.gpb.2016.12.005.
[14] Wang P, Xue Y, Han Y, et al. The STAT3-binding long noncoding RNA lnc-DC controls human dendritic cell differentiation [J]. Science, 2014, 344(6181): 310-313.
[15] Xin J, Li J, Feng Y, et al. Downregulation of long noncoding RNA HOTAIRM1 promotes monocyte/dendritic cell differentiation through competitivel binding to endogenous miR-3960 [J]. Onco Targets Ther, 2017, 10: 1307-1315. doi: 10.2147/OTT.S124201.
[16] Fang P, Xiang L, Chen W, et al. LncRNA GAS5 enhanced the killing effect of NK cell on liver cancer through regulating miR-544/RUNX3 [J]. Innate Immun, 2019, 25(2): 99-109.
[17] Chang L, Li C, Lan T, et al. Decreased expression of long non-coding RNAGAS5 indicates a poor prognosis and promotescell proliferation and invasion in hepatocellular carcinoma by regulating vimentin [J]. Mol Med Rep, 2016, 13(2): 1541-1550.
[18] Tian X, Wu Y, Yang Y. Long noncoding RNA LINC00662 promotes M2 macrophage polarization and Hepatocellular carcinoma progression via activating Wnt/beta-catenin signaling [J]. Mol Oncol, 2020, 14(2): 462-483.
[19] Liu J, Ding D, Jiang Z, et al. Long non-coding RNA CCAT1/miR-148a/PKCzet prevents cell migration of prostate cancerby altering macrophage polarization [J]. Prostate, 2019, 79(1): 105-112.
[20] Zhang L, Li C, Su X. Emerging impact of the long noncoding RNA MIR22HG and apoptosis in multiple human cancers [J]. J Exp Clin Cancer Res, 2020, 39(1): 271. doi:10.1186/s13046-020-01784-8.
[21] Zhou L, Zhu Y, Sun D, et al. Emerging roles of Long non-coding RNAs in the tumor microenvironment [J]. Int J Biol Sci, 2020, 16(12): 2094-2103.
[22] Wang Y, Battseren B, Yin W, et al. Predictive and prognostic value of prognostic nutritional index for locally advanced breast cancer [J]. Gland Surg, 2019, 8(6): 618-626.
[23] Ma W, Zhao F, Yu X, et al. Immune-related lncRNAs as predictors of Survival in breast cancer: a prognostic signature [J]. J Transl Med, 2020, 18(1): 442. doi:10.1186/s12967-020-02522-6.
[24] 吴彬, 姚颐, 董熠, 等.构建结肠癌免疫相关长链非编码RNA风险评分模型[J].肿瘤学杂志, 2020, 26(11): 966-971. WU Bin, YAO Yi, DONG Yi, et al. Construction of risk score nodel for prognosis of colon cancer with immune-related long non-coding RNA[J]. Journal of Chinese Oncology, 2020, 26(11): 966-971.
[25] 底斐瑶, 王一鹤, 底泽亚, 等.基于TCGA数据库确定宫颈癌预后免疫相关性长链非编码RNA并构建预后模型[J].世界最新医学信息文摘, 2020, 20(87): 34-39. DI Feiyao, WANG Yihe, DI Zeya, et al. Identifying immune-related lncRNA and constructing prognostic model in cervical cancer patients based on TCGA database[J]. World Latest Medicine Informatio(Electronic Version), 2020, 20(87): 34-39.
[26] 陈晓旭, 于洋, 张天雪. 基于免疫相关lncRNA 建立胰腺癌预后风险评估模型[J].国际肿瘤学杂志, 2020, 47(8): 472-479. CHEN Xiaoxu, YU Yang, ZHANG Tianxue. Aprognosis crisk assessment model for pancreatic cancer stablished based on immune related lncRNAs[J]. Journal of International Oncology, 2020, 47(8): 472-479.
[27] 王尧, 周旻, 柳子川, 等.免疫相关LncRNA与膀胱癌预后关系分析及预测模型建立[J].遵义医科大学学报, 2020, 43(1): 76-80. WANG Yao, ZHOU Min, LIU Zichuan, et al. Analysis of prognostic immune-related lncRNA and development of prognostic model for bladder cancer patients[J]. Journal of Zunyi Medical University, 2020, 43( 1): 76-80.
[1] 徐平 于国放 李霞. 不同类型甲状腺上动脉PSV对Graves病与桥本氏甲状腺炎鉴别诊断的价值[J]. 山东大学学报(医学版), 2209, 47(6): 62-64.
[2] 黄方 康瑞 吴春林. VEGFC、NF-κBp65及Survivin在鼻咽癌中的表达及临床意义[J]. 山东大学学报(医学版), 2209, 47(6): 83-.
[3] 王欣,邢春燕,杨艳平. 血清磷酸丙酮酸水合酶检测对诊断侵袭性白念珠菌感染的临床价值[J]. 山东大学学报(医学版), 2209, 47(6): 92-94.
[4] 闫鹏 王蓉 杜怡峰 沈伦乾. 老年性痴呆患者尿中AD7c-NTP含量的研究[J]. 山东大学学报(医学版), 2209, 47(6): 106-.
[5] 吴志晓,赵红洋. 孟德尔随机化分析免疫细胞表型与孤独症谱系障碍的因果关联[J]. 山东大学学报 (医学版), 2026, 64(3): 83-92.
[6] 王建民,李晓峰,由志涛,董圣杰,赵宇驰,李占菊,邹德鑫,张剑锋,孙涛,杜伟. 基于可解释机器学习的后路腰椎椎体间融合术后慢性疼痛风险预测模型构建[J]. 山东大学学报 (医学版), 2026, 64(2): 78-88.
[7] 古春青,郭睿思,周勤勤,刘恒辉,巴婉玉,孙士玲,王冰,郑玉玲,吴宿慧. 基于网络药理学和动物实验探讨酸枣仁-远志药对治疗乳腺癌相关性失眠的作用机制[J]. 山东大学学报 (医学版), 2026, 64(1): 99-108.
[8] 孙爽爽,仉率杰,张伯韬,袁莹,于媛媛,薛付忠. 基于真实世界研究的18~50岁人群急性缺血性卒中影响因素[J]. 山东大学学报 (医学版), 2025, 63(9): 40-46.
[9] 李梓绮,魏闫若雪,刘晓晗,刘春铖,赵然,刘玉昆. 长链非编码RNA HEATR3反义RNA 1参与结直肠癌发生发展的功能及其临床意义[J]. 山东大学学报 (医学版), 2025, 63(9): 108-115.
[10] 申路佳,逯天威,巩伟明,赵岩松,王淑康,袁中尚. 代谢风险评分在2型糖尿病人群心血管结局预测中的应用[J]. 山东大学学报 (医学版), 2025, 63(8): 69-78.
[11] 张政,王建伟,杨玉娟,张宇,宋西成. 哮喘儿童2008及2019年免疫球蛋白E变化及相关危险因素[J]. 山东大学学报 (医学版), 2025, 63(7): 32-36.
[12] 刘保国,宋翔,赵晓文,毛亚丽. 血清STAT5B、NKAIN1 mRNA检测在乳腺癌中的应用价值[J]. 山东大学学报 (医学版), 2025, 63(7): 68-74.
[13] 王磊,常霄,王梓萌,李娇娇,崔书君,杨飞,朱月香. 瘤内及瘤周DCE-MRI影像组学对宫颈癌患者无进展生存期的预测价值[J]. 山东大学学报 (医学版), 2025, 63(6): 45-54.
[14] 王丽云,高天勤,刘雨佳,陈青,陈柳,沙凯辉. 基于机器学习产后压力性尿失禁风险预测模型的构建及验证[J]. 山东大学学报 (医学版), 2025, 63(6): 55-66.
[15] 王雪梅,杨豪,宋洋,程世超,张婷婷,王艳春. 抗糖尿病药物与女性恶性肿瘤的因果关联:一项两样本孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(6): 67-77.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!