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8-自噬相关lncRNA模型在预测膀胱癌患者预后中的作用
Role of 8-autophagy-related long non-coding RNAs signature in prognosis for bladder cancer
- 第三军医大学学报 2021年43卷第23期 页码：2532-2541
- 作者机构：
1.400016 重庆，重庆医科大学附属第一医院泌尿外科
2.402460 重庆，重庆市荣昌中医院泌尿外科
3.402760 重庆，重庆市璧山中医院泌尿外科
- 作者简介：
[何卫阳，E-mail: weiyang361@aliyun.com HE Weiyang, E-mail: weiyang361@aliyun.com
- 基金信息：
DOI：10.16016/j.1000-5404.202106120
中图分类号： R181.23;R730.7;R737.14收稿：2021-06-16，
修回：2021-09-21，
纸质出版：2021-12-15
- 稿件说明：
移动端阅览
童行, 李庭浩, 曹洪豪, 等. 8-自噬相关lncRNA模型在预测膀胱癌患者预后中的作用[J]. 第三军医大学学报, 2021,43(23):2532-2541.
Hang TONG, Tinghao LI, Honghao CAO, et al. Role of 8-autophagy-related long non-coding RNAs signature in prognosis for bladder cancer[J]. Journal of Third Military Medical University, 2021, 43(23): 2532-2541.
童行, 李庭浩, 曹洪豪, 等. 8-自噬相关lncRNA模型在预测膀胱癌患者预后中的作用[J]. 第三军医大学学报, 2021,43(23):2532-2541. DOI： 10.16016/j.1000-5404.202106120.
Hang TONG, Tinghao LI, Honghao CAO, et al. Role of 8-autophagy-related long non-coding RNAs signature in prognosis for bladder cancer[J]. Journal of Third Military Medical University, 2021, 43(23): 2532-2541. DOI： 10.16016/j.1000-5404.202106120.
摘要
目的
2
探究自噬相关lncRNA风险预测模型在膀胱癌患者中的潜在预后作用与价值。
方法
2
从TCGA数据库中获取膀胱癌患者的转录组数据和相应的临床资料。通过R软件将402例膀胱癌样本按3 ∶1的比例随机分为训练集及验证集。通过Pearson相关性分析筛选自噬相关lncRNA，并通过单因素和多因素Cox回归分析构建自噬相关lncRNA预后模型。通过绘制ROC曲线评估模型的准确性。进一步计算样本风险评分并分析其与患者临床特征、生存预后的关系。另外通过构建列线图评估该模型对膀胱癌患者预后的预测能力。最后，通过GSEA分析不同风险分组可能富集的KEGG通路。采用RT-qPCR验证模型中高危lncRNA的表达情况。
结果
2
成功构建了一个8-自噬相关lncRNA模型，在训练集、验证集和总体集中，该预后模型ROC曲线的AUC值均大于0.75。模型风险评分与患者年龄、AJCC分期和T分期有关(
P
<
0.05)，与患者性别无明显关系。通过整合临床变量和风险评分建立的列线图证实该模型具有良好的预后预测能力。GSEA分析显示，一些肿瘤和自噬相关通路在高风险组富集，而免疫相关通路在低风险组富集。模型中lncRNA AC005229.4在膀胱癌细胞系中高表达。
结论
2
8-自噬相关lncRNA模型对膀胱癌患者的预后具有较好的预测效能。
Abstract
Objective
2
To explore the potential prognostic role and value of autophagy-related lncRNA risk prediction signature in patients with bladder cancer.
Methods
2
The transcriptome data and corresponding clinical data of patients with bladder cancer were obtained from the Cancer Genome Atlas (TCGA) database. Four hundreds and two bladder cancer samples were randomly divided into training set and verification set according to the ratio of 3 ∶1 by R software. Autophagy-related lncRNA
was screened by Pearson correlation analysis
and autophagy-related lncRNA prognostic signature was constructed by univariate and multivariate Cox regression analyses. The accuracy of the signature was evaluated by drawing ROC curve. The sample risk score was further calculated
and the relationship of the sample risk score with clinical characteristics and survival prognosis was analyzed. In addition
the ability of the signature to predict the prognosis of patients with bladder cancer was evaluated by constructing a nomogram. Finally
the possible enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis in different risk groups were analyzed by gene set enrichment analysis (GSEA). Finally
the expression of high-risk lncRNA was verified in the signature by RT-qPCR.
Results
2
An 8-autophagy-related lncRNA signature was successfully constructed. In the training set
validation set and whole set
the AUC values of the ROC curve of the prognostic signature were all greater than 0.75. The risk score of the signature was related to age
American Joint Committee on Cancer (AJCC) stage and T stage of the patients (
P
<
0.05)
but not to their gender. The nomogram established by integrating clinical variables and risk scores confirmed that the signature had a good ability to predict prognosis. GSEA showed that some tumor and autophagy-related pathways were enriched in the high-risk group
while immune-related pathways were enriched in the low-risk group. lncRNA AC005229.4 was highly expressed in bladder cancer cell lines.
Conclusion
2
An 8-autophagy-related lncRNA signature is effective in the prognostic prediction of patients with bladder cancer.
关键词
Keywords
references
ROBERTSON A G, KIM J, AL-AHMADIE H, et al . Comprehensive molecular characterization of muscle-invasive bladder cancer[J ] . Cell, 2017, 171 (3): 540-556.e25. DOI: 10.1016/j.cell.2017.09.007.
LENIS A T, LEC P M, CHAMIE K, et al . Bladder cancer: a review[J ] . JAMA, 2020, 324(19): 1980-1991. DOI: 10.1001/jama.2020.17598.
张敏, 周丽娜, 徐姗姗, 等. 肿瘤免疫治疗相关预测生物标志物研究进展[J]. 国际肿瘤学杂志, 2020, 47 (8): 487-491.
ZHANG M. ZHOU L N, XU S S, et al . Research progress in predictive biomarkers related to tumorimmunotherapy[J ] . J Int Oncol, 2020, 47 (8): 487-491.
LEVY J M M, TOWERS C G, THORBURN A. Targeting autophagy in cancer[J]. Nat Rev Cancer, 2017, 17(9): 528-542. DOI: 10.1038/nrc.2017.53.
TONG H, YIN H B, HOSSAIN M A, et al . Starvation-induced autophagy promotes the invasion and migration of human bladder cancer cells via TGF-β1/Smad3-mediated epithelial-mesenchymal transition activation[J ] . J Cell Biochem, 2019, 120(4): 5118-5127. DOI: 10.1002/jcb.27788..
YANG X Y, YIN H B, ZHANG Y Z, et al . Hypoxia-induced autophagy promotes gemcitabine resistance in human bladder cancer cells through hypoxia-inducible factor 1α activation[J ] . Int J Oncol, 2018, 53 (1): 215-224. DOI: 10.3892/ijo.2018.4376.
TIAN X, XU W, WANG Y, et al . Identification of tumor-infiltrating immune cells and prognostic validation of tumor-infiltrating mast cells in adrenocortical carcinoma: results from bioinformatics and real-world data[J ] . Oncoimmunology, 2020, 9(1): 1784529. DOI: 10.1080/2162402x.2020.1784529.
FLIPPOT R, BEINSE G, BOILÈVE A, et al . Long non-coding RNAs in genitourinary malignancies: a whole new world[J ] . Nat Rev Urol, 2019, 16(8): 484-504. DOI: 10.1038/s41585-019-0195-1.
NG K, STENZL A, SHARMA A, et al . Urinary biomarkers in bladder cancer: a review of the current landscape and future directions[J ] . Urol Oncol, 2021, 39(1): 41-51. DOI: 10.1016/j.urolonc.2020.08.016.
CHENG M L, IYER G. Novel biomarkers in bladder cancer[J]. Urol Oncol, 2018, 36(3): 115-119. DOI: 10.1016/j.urolonc.2018.01.009.
MATI Q, QAMAR S, ASHRAF S, et al . Tissue nuclear matrix protein expression 22 in various grades and stages of bladder cancer[J ] . J Coll Physicians Surg Pak, 2020, 30(12): 1321-1325. DOI: 10.29271/jcpsp.2020.12.1321.
LI X, SHU K P, ZHOU J, et al . Preoperative plasma fibrinogen and D-dimer as prognostic biomarkers for non-muscle-invasive bladder cancer[J ] . Clin Genitourin Cancer, 2020, 18(1): 11-19.e1. DOI: 10.1016/j.clgc.2019.10.025.
ANASTASIADOU E, JACOB L S, SLACK F J. Non-coding RNA networks in cancer[J]. Nat Rev Cancer, 2018, 18(1): 5-18. DOI: 10.1038/nrc.2017.99.
CHEN C H, LUO Y M, HE W, et al . Exosomal long noncoding RNA LNMAT2 promotes lymphatic metastasis in bladder cancer[J ] . J Clin Investig, 2020, 130(1): 404-421. DOI: 10.1172/JCI130892.
ZHENG R, DU M L, WANG X W, et al . Exosome-transmitted long non-coding RNA PTENP 1 suppresses bladder cancer progression[J ] . Mol Cancer, 2018, 17(1): 143. DOI: 10.1186/s12943-018-0880-3..
SHEN D Y, ZHANG Y Y, ZHENG Q M, et al . A competing endogenous RNA network and an 8-lncRNA prognostic signature identify MYO16-AS1 as an oncogenic lncRNA in bladder cancer[J ] . DNA Cell Biol, 2021, 40(1): 26-35. DOI: 10.1089/dna.2020.6014.
TONG H, LI T H, GAO S, et al . An epithelial-mesenchymal transition-related 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.
ZHAO D, PENG Q, WANG L, et al . Identification of a six-lncRNA signature based on a competing endogenous RNA network for predicting the risk of tumour recurrence in b ladder cancer patients[J ] . J Cancer, 2020, 11(1): 108-120. DOI: 10.7150/jca.35801.
AMARAVADI R K, KIMMELMAN A C, DEBNATH J. Targeting autophagy in cancer: recent advances and future directions[J]. Cancer Discov, 2019, 9(9): 1167-1181. DOI: 10.1158/2159-8290.CD-19-0292.
童行, 何卫阳. 自噬在肿瘤上皮-间充质转化以及侵袭转移中的作用[J]. 现代泌尿外科杂志, 2019, 24(5): 404-408.
TONG H, HE W Y. Research progress on the role of autophagy in the invasion and metastasis of epithelial-mesenchymal transition[J]. J Mod Urol, 2019, 24(5): 404-408.
WANG S S, CHEN G, LI S H, et al . Identification and validation of an individualized autophagy-clinical prognostic index in bladder cancer patients[J ] . Onco Targets Ther, 2019, 12: 3695-3712. DOI: 10.2147/ott.s197676.
BALACHANDRAN V P, GONEN M, SMITH J J, et al . Nomograms in oncology: more than meets the eye[J ] . Lancet Oncol, 2015, 16(4): e173-e180. DOI: 10.1016/s1470-2045(14)71116-7.
KIYONO K, SUZUKI H I, MATSUYAMA H, et al . Autophagy is activated by TGF-beta and potentiates TGF-beta-mediated growth inhibition in human hepatocellular carcinoma cells[J ] . Cancer Res, 2009, 69(23): 8844-8852. DOI: 10.1158/0008-5472.CAN-08-4401.
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