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中华腔镜泌尿外科杂志(电子版) ›› 2025, Vol. 19 ›› Issue (03) : 315 -322. doi: 10.3877/cma.j.issn.1674-3253.2025.03.006

临床研究

膀胱尿路上皮癌血管生成相关LncRNA预后评估模型的构建与分析
龙朝辉1,2, 陈丹2, 王依杰2, 瞿根义2, 徐勇1,2,(), 阳光2, 黄文琳2, 汤乘2   
  1. 1. 412007 湖南,吉首大学株洲临床学院
    2. 412007 湖南,中南大学湘雅医学院附属株洲医院泌尿外科
  • 收稿日期:2024-03-08 出版日期:2025-06-01
  • 通信作者: 徐勇
  • 基金资助:
    湖南省自然科学基金项目(2021JJ41094)

Construction and analysis of a prognostic assessment model of angiogenesis related LncRNA in bladder urothelial cancer

Zhaohui Long1,2, Dan Chen2, Yijie Wang2, Genyi Qu2, Yong Xu1,2,(), Guang Yang2, Wenlin Huang2, Cheng Tang2   

  1. 1. Zhuzhou Clinical College, Jishou University,Zhuzhou 412007, China
    2. Department of Urology, Zhuzhou Hospital Affiliated to Xiangya School ofMedicine, Central South University, Zhuzhou 412007, China
  • Received:2024-03-08 Published:2025-06-01
  • Corresponding author: Yong Xu
引用本文:

龙朝辉, 陈丹, 王依杰, 瞿根义, 徐勇, 阳光, 黄文琳, 汤乘. 膀胱尿路上皮癌血管生成相关LncRNA预后评估模型的构建与分析[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(03): 315-322.

Zhaohui Long, Dan Chen, Yijie Wang, Genyi Qu, Yong Xu, Guang Yang, Wenlin Huang, Cheng Tang. Construction and analysis of a prognostic assessment model of angiogenesis related LncRNA in bladder urothelial cancer[J/OL]. Chinese Journal of Endourology(Electronic Edition), 2025, 19(03): 315-322.

目的

探讨血管生成相关长链非编码RNA(LncRNA)在膀胱尿路上皮癌(BLCA)中的预后作用,并建立BLCA 血管生成相关LncRNA 预后评估模型。

方法

从TCGA 数据库下载BLCA 的RNA 测序和临床数据,从分子特征数据库获取最新人类血管生成基因列表,计算每个LncRNA 与每个血管生成基因的相关系数,获得与血管生成基因显著相关的LncRNA,使用R 软件对每个LncRNA 进行单因素和多因素Cox 回归分析,结合Kaplan-Meier 法筛选与BLCA 预后相关的LncRNA,绘制相关LncRNA 与BLCA 患者生存期的Kaplan-Meier 曲线,计算每个样本的风险评分,根据评分将样本分为高风险组和低风险组,比较两组患者的生存期差异,绘制ROC 曲线评估模型预测效能,采用Cox 回归分析风险评分和患者临床特征与生存期的相关性。

结果

初筛识别了207 个与BLCA 血管生成相关的LncRNA(相关系数|R|>0.4,P<0.001)。进一步通过Cox 回归分析,筛选出9 个与BLCA 预后独立相关的血管生成相关LncRNA,用于建立BLCA 预后评估模型。根据该模型将患者分为高风险组和低风险组,高风险组患者生存期显著短于低风险组(P<0.05)。模型ROC曲线下面积为0.716,表明模型具有较好的预测效能。风险评分与患者年龄、肿瘤分级、病理分期及T分期呈正相关(P<0.05),是BLCA 的独立预后预测因子。

结论

基于血管生成相关LncRNA 的预后评估模型,可为BLCA 患者提供精准的预后判断,有助于指导BLCA 的个体化治疗方案选择和预后评估。

Objective

To investigate the prognostic role of long non-coding RNA (LncRNA)in bladder urothelial carcinoma (BLCA) and to establish a prognostic assessment model of BLCA angiogenesis-associated LncRNA.

Methods

The RNA sequencing and clinical data of BLCA were downloaded from the TCGA database, and the latest list of human angiogenesis genes was obtained from the molecular characteristics database.The correlation coefficient between each LncRNA and each angiogenesis gene was calculated, and LncRNA significantly correlated with angiogenesis genes were obtained.Univariate and multivariate Cox regression analysis was performed for each LncRNA using R software, and the LncRNA associated with BLCA prognosis was screened by Kaplan-Meier method.Kaplan-Meier curves of survival time of relevant LncRNA and BLCA patients were drawn, and the risk score of each sample was calculated.According to the score, the samples were divided into high-risk group and low-risk group, and the differences in survival between the two groups were compared.The ROC curve was drawn to evaluate the predictive ability of the model, and Cox regression was used to analyze the correlation between the risk score and patients' clinical characteristics and survival.

Results

Initial screening identified 207 LncRNA associated with BLCA angiogenesis (correlation coefficient |R|>0.4,P<0.001).Cox regression analysis was used to select 9 angiogenesis-related LncRNA that independently correlated with BLCA prognosis to establish a prognostic assessment model for BLCA.According to the model, patients were divided into high-risk and low-risk groups, and the survival of patients in the high-risk group was significantly shorter than that in the low-risk group (P<0.05).The area under the ROC curve of the model is 0.716, indicating that the model has good predictive efficiency.The risk score was positively correlated with age, tumor grade, pathological stage and T stage (P<0.05) and was an independent prognostic predictor of BLCA.

Conclusion

The prognostic assessment model based on LncRNA associated with angiogenesis can provide accurate prognostic assessment for BLCA patients and help guide individualized treatment selection and prognostic assessment for BLCA patients.

图1 膀胱尿路上皮癌(BLCA)预后评估模型中9 个血管生成相关 LncRNA 的生存曲线
图2 9 个血管生成相关LncRNA 与血管生成相关基因系对BLCA 预后影响的桑基图 图3 BLCA 预后评估模型(风险评分)特征和基因热图 图4 高、低风险组BLCA 患者生存曲线 图5 BLCA 预后评估模型的ROC 曲线 图6 BLCA 患者临床病理参数和风险评分Cox 回归分析森林图 注:3a 为BLCA 患者风险评分分布图;3b 为高风险组和低风险组患者生存状态;3c 为9 个血管生成相关LncRNA 基因热图;6a 为单因素Cox 分析;6b 为多因素Cox 分析;BLCA 为膀胱尿路上皮癌
表1 膀胱尿路上皮癌(BLCA)预后评估模型中9 个血管生成相关LncRNA
表2 预后评估模型与167 例膀胱尿路上皮癌(BLCA)患者临床病理特征的关系
[1]
Siegel RL, Miller KD, Fuchs HE, et al.Cancer statistics, 2022[J].CA A Cancer J Clinicians, 2022, 72(1): 7-33.DOI: 10.3322/caac.21708.
[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.DOI: 10.3322/caac.21492.
[3]
Richters A, Aben KKH, Kiemeney LALM.The global burden of urinary bladder cancer: an update[J].World J Urol, 2020, 38(8):1895-1904.DOI: 10.1007/s00345-019-02984-4.
[4]
Hanahan D, Weinberg RA.Hallmarks of cancer: the next generation[J].Cell, 2011, 144(5): 646-674.DOI: 10.1016/j.cell.2011.02.013.
[5]
Lin X, Yang F, Qi X, et al.LncRNA DANCR promotes tumor growth and angiogenesis in ovarian cancer through direct targeting of miR-145[J].Mol Carcinog, 2019, 58(12): 2286-2296.DOI: 10.1002/mc.23117.
[6]
Huang QY, Liu GF, Qian XL, et al.Long non-coding RNA: dual effects on breast cancer metastasis and clinical applications[J].Cancers (Basel), 2019, 11(11): 1802.DOI: 10.3390/cancers11111802.
[7]
莫碧瑶,肖璐,詹宇威,等.长链非编码RNA GAPLINC 对类风湿关节炎成纤维样滑膜细胞增殖表型的影响[J].中山大学学报(医学科学版), 2023, 44(5): 792-800.DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0510.Mo BY, Xiao L, Zhan YW, et al.Effects of long non-coding RNA GAPLINC on the proliferative phenotype of fibroblast-like synoviocytes in rheumatoid arthritis[J].J Sun Yat-sen Univ (Med Sci), 2023, 44(5): 792-800.DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2023.0510.
[8]
罗铿军, 张文波, 蒋鹏程.长链非编码RNA 参与调控肿瘤中髓源性抑制细胞的研究进展[J].实用医学杂志, 2024, 40(18): 2647-2653.DOI: 10.3969/j.issn.1006-5725.2024.18.024.Luo KJ, Zhang WB, Jiang PC.Research progress on long noncoding RNA regulating myeloid-derived suppressor cells in tumors[J].J Pract Med, 2024, 40(18): 2647-2653.DOI: 10.3969/j.issn.1006-5725.2024.18.024.
[9]
张锋, 王聪, 朱明霞, 等.丹酚酸A 调控 LncRNA TSPOAP1-AS1 缓解H2O2 诱导脑微血管内皮细胞凋亡及血管新生能力的影响[J].解剖学研究, 2024, 46(4): 375-383.DOI: 10.20021/j.cnki.1671-0770.2024.04.12.Zhang F, Wang C, Zhu MX, et al.Salvianolic acid A alleviates H2O2-induced apoptosis and angiogenesis impairment in cerebral microvascular endothelial cells by regulating LncRNA TSPOAP1-AS1[J].Anat Res, 2024, 46(4): 375-383.DOI: 10.20021/j.cnki.1671-0770.2024.04.12.
[10]
Zhao J, Li L, Han ZY, et al.Long noncoding RNAs, emerging and versatile regulators of tumor-induced angiogenesis[J].Am J Cancer Res, 2019, 9(7): 1367-1381.
[11]
Lin J, Cao S, Wang Y, et al.Long non-coding RNA UBE2CP3 enhances HCC cell secretion of VEGFA and promotes angiogenesis by activating ERK1/2/HIF-1α/VEGFA signalling in hepatocellular carcinoma[J].J Exp Clin Cancer Res, 2018, 37(1): 113.DOI:10.1186/s13046-018-0727-1.
[12]
Lv M, Zhong Z, Huang M, et al.lncRNA H19 regulates epithelialmesenchymal transition and metastasis of bladder cancer by miR-29b-3p as competing endogenous RNA[J].Biochim Biophys Acta Mol Cell Res, 2017, 1864(10): 1887-1899.DOI: 10.1016/j.bbamcr.2017.08.001.
[13]
Alfred Witjes J, Bruins HM, Carrión A, et al.European association of urology guidelines on muscle-invasive and metastatic bladder cancer:summary of the 2023 guidelines[J].Eur Urol, 2024, 85(1): 17-31.DOI: 10.1016/j.eururo.2023.08.016.
[14]
曹明远, 张振东, 侯鑫睿, 等.非编码RNA 调控消化道肿瘤铁死亡的分子机制研究进展[J].暨南大学学报(自然科学与医学版),2024, 45(4): 348-356, 437.DOI: 10.11778/j.jdxb.20240051.Cao MY, Zhang ZD, Hou XR, et al.Research progress on the molecular mechanism of non-coding RNA regulating ferroptosis in digestive tract tumors[J].J Jinan Univ Nat Sci Med Ed, 2024, 45(4):348-356, 437.DOI: 10.11778/j.jdxb.20240051.
[15]
刘芳, 金日群, 段佳丽, 等.长链非编码RNA CCAT1 在喉鳞状细胞癌的表达及其意义[J].广东医学, 2023, 44(3): 336-339.DOI:10.13820/j.cnki.gdyx.20223571.Liu F, Jin RQ, Duan JL, et al.Expression and significance of long non-coding RNA CCAT1 in laryngeal squamous cell carcinoma[J].Guangdong Med J, 2023, 44(3):336-339.DOI: 10.13820/j.cnki.gdyx.20223571.
[16]
杨靖瑞, 高榴, 许颖, 等.长链非编码RNA NBR2 在乳腺癌患者血清中的表达水平及临床意义[J].热带医学杂志, 2023, 23(7):890-894.DOI: 10.3969/j.issn.1672-3619.2023.07.002.Yang JR, Gao L, Xu Y, et al.Expression and clinical significance of serum long non-coding RNA NBR2 in breast cancer patients[J].J Trop Med, 2023, 23(7): 890-894.DOI: 10.3969/j.issn.1672-3619.2023.07.002.
[17]
Pencik J, Pham HT, Schmoellerl J, et al.JAK-STAT signaling in cancer: From cytokines to non-coding genome[J].Cytokine, 2016,87: 26-36.DOI: 10.1016/j.cyto.2016.06.017.
[18]
Abdollahzadeh R, Daraei A, Mansoori Y, et al.Competing endogenous RNA (CeRNA) cross talk and language in CeRNA regulatory networks: a new look at hallmarks of breast cancer[J].J Cell Physiol, 2019, 234(7): 10080-10100.DOI: 10.1002/jcp.27941.
[19]
Li Y, Zu X, Hu X, et al.Competing endogenous RNA network analysis reveals pivotal ceRNAs in bladder urothelial carcinoma[J].Transl Androl Urol, 2021, 10(2): 797-808.DOI: 10.21037/tau-20-1167.
[20]
陈欣欣, 陈晓隆.长链非编码RNA 与微RNA 相互作用在血管生成中的研究进展[J].中国医科大学学报, 2023, 52(5): 457-460.DOI: 10.12007/j.issn.0258-4646.2023.05.013 Chen XX, Chen XL.Research progress on the interaction between long non-coding RNA and microRNA in angiogenesis[J].J China Med Univ, 2023, 52(5): 457-460.DOI: 10.12007/j.issn.0258-4646.2023.05.013
[21]
Yu Z, Deng H, Chao H, et al.Construction of a cuproptosisrelated lncRNA signature to predict biochemical recurrence of prostate cancer[J].Oncol Lett, 2024, 28(5): 526.DOI: 10.3892/ol.2024.14659.
[22]
Tong H, Li T, Gao S, et al.An epithelial-mesenchymal transitionrelated long noncoding RNA signature correlates with the prognosis and progression in patients with bladder cancer[J].Biosci Rep, 2021,41(1): BSR20203944.DOI: 10.1042/BSR20203944.
[23]
Chen M, Nie Z, Li Y, et al.A new ferroptosis-related lncRNA signature predicts the prognosis of bladder cancer patients[J].Front Cell Dev Biol, 2021, 9: 699804.DOI: 10.3389/fcell.2021.699804.
[24]
Guo ZH, Yao LT, Guo AY.Clinical and biological impact of LINC02544 expression in breast cancer after neoadjuvant chemotherapy[J].Eur Rev Med Pharmacol Sci, 2020, 24(20): 10573-10585.DOI: 10.26355/eurrev_202010_23413.
[25]
Wu ZH, Gong YW, Zhao LQ, et al.Silencing of LncRNA C1RLAS1 suppresses the malignant phenotype in gastric cancer cells via the AKT/β-catenin/c-myc pathway[J].Front Oncol, 2020, 10: 1508.DOI: 10.3389/fonc.2020.01508.
[26]
Li RH, Tian T, Ge QW, et al.A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling[J].Cell Res, 2021, 31(10): 1088-1105.DOI: 10.1038/s41422-021-00530-9.
[27]
Cheng Y, Ping J, Chen J, et al.Molecular mechanism of atractylon in the invasion and migration of hepatic cancer cells based on highthroughput sequencing[J].Mol Med Rep, 2022, 25(4): 112.DOI:10.3892/mmr.2022.12628.
[28]
Li C, Liang X, Liu Y.lncRNA USP30-AS1 sponges miR-765 and modulates the progression of colon cancer[J].World J Surg Oncol,2022, 20(1): 73.DOI: 10.1186/s12957-022-02529-x.
[29]
瞿根义, 向茂林, 徐勇, 等.膀胱尿路上皮癌自噬相关LncRNA预后风险模型的建立与分析[J].临床泌尿外科杂志, 2021, 36(7):523-527.DOI: 10.13201/j.issn.1001-1420.2021.07.004.Qu GY, Xiang ML, Xu Y, et al.Establishment and analysis of prognostic risk model of autophagy-related LncRNA in bladder urothelial carcinoma[J].J Clin Urol, 2021, 36(7): 523-527.DOI:10.13201/j.issn.1001-1420.2021.07.004.
[30]
单卫民, 管波.基于膀胱尿路上皮癌免疫相关基因预后模型的建立与验证[J].现代泌尿生殖肿瘤杂志, 2021, 13(6): 325-329.DOI:10.3870/j.issn.1674-4624.2021.06.002.Shan WM, Guan B.Establishment and validation of prognosis signature of bladder urothelial carcinoma based on immune re-lated genes[J].J Contemp Urol Reprod Oncol, 2021, 13(6): 325-329.DOI:10.3870/j.issn.1674-4624.2021.06.002.
[31]
Hou J, Lu Z, Dong R, et al.A necroptosis-related lncRNA to develop a signature to predict the outcome, immune landscape, and chemotherapeutic responses in bladder urothelial carcinoma[J].Front Oncol, 2022, 12: 928204.DOI: 10.3389/fonc.2022.928204.
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