Correlation analysis of mir-15a and postoperative recurrence amongst patients with bladder carcinoma
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摘要:
目的 探讨miR-15a表达水平在膀胱癌进展及与膀胱癌患者术后复发的相关性。 方法 选取2014年6月—2019年12月于蚌埠医学院第一附属医院泌尿外科接受经尿道膀胱肿瘤等离子电切术(TURBT)的32例确诊为膀胱癌的患者。膀胱癌组织取自肿瘤所在部位区域,癌旁组织取自邻近正常区域组织;应用实时定量聚合酶链反应(qRT-PCR)技术检测膀胱癌组织标本或癌旁组织标本中miR-15a表达量;采用Kaplan-Meier法描述术后预后曲线,组间比较采用log-rank检验;采用χ2检验比较膀胱癌组织及配对的癌旁组织中miR-15a表达水平及一般临床特征等因素的差异;采用多因素logistic回归分析研究肌层浸润、远处转移及肿瘤分级等临床病理特征与miR-15a表达水平的关系。 结果 miR-15a在膀胱癌组织中表达量明显低于配对的癌旁组织(1.126±0.254 vs. 1.450±0.139),差异具有统计学意义(P < 0.001);miR-15a表达水平与肌层浸润(P=0.001)、远处转移(P=0.005)及肿瘤分级状态具有显著相关性(P=0.027);log-rank检验证明miR-15a表达水平下调的患者总体复发率较高,差异具有统计学意义(P=0.023);多因素logistic回归分析显示,远处转移为阳性、肌层浸润(T2~T4)、肿瘤分级为G3是miR-15a表达水平下调的独立危险因素。 结论 miR-15a表达水平可能与膀胱癌的发生及发展密切相关,其表达水平与肌层浸润、远处转移及肿瘤分级显著相关,可能是膀胱肿瘤复发的生物标志物。 -
关键词:
- 膀胱癌 /
- 非编码小分子RNA-15a /
- 复发 /
- 肌层浸润 /
- 表达水平
Abstract:Objective This study aimed to investigate the correlation between the miR-15a expression level and progression of bladder cancer and postoperative recurrence in patients with bladder cancer. Methods Thirty-two patients diagnosed with bladder cancer who underwent transurethral plasma resection of bladder tumour transurethral resection of bladder tumour (TURBT) in the Department of Urology of the First Affiliated Hospital of Bengbu Medical College from June 2014 to December 2019 were enrolled in this study. Bladder cancer tissue was obtained from the tumour site, whereas paracancerous tissue was obtained from the adjacent normal area. Real-time quantitative polymerase chain reaction was used to detect the expression of miR-15a in bladder cancer tissue samples or paracancerous tissue samples. The Kaplan-Meier method was used to describe the postoperative prognosis curve, and log-rank test was used for comparison amongst groups. The χ2-test test was used to compare the differences in the expression level and general clinical characteristics of miR-15a in bladder cancer tissues and matched paracancerous tissues. Multivariate logistic regression analysis was used to describe the clinicopathological features such as muscular invasion, distant metastasis and tumour grade. Results The expression level of miR-15a in bladder cancer tissues was significantly lower than that in adjacent tissues (1.126±0.254 vs 1.450±0.139), and the difference was statistically significant (P < 0.001). In addition, the miR-15a expression level was significantly correlated with muscular invasion (P=0.001), distant metastasis (P=0.005) and tumour grade (P=0.027). Log-rank test showed that patients with down-regulated miR-15a expression had a higher overall recurrence rate, and the difference was statistically significant (P=0.023). Multivariate logistic regression analysis showed that positive distant metastasis, muscular invasion (T2-T4) and tumour grade G3 were independent risk factors for the down-regulation of miR-15a expression. Conclusion The expression level of miR-15a may be closely related to the occurrence and development of bladder cancer, and its expression level is significantly correlated with muscular invasion, distant metastasis and tumour grade. The down-regulated expression level of miR-15a may be a biomarker for bladder tumour recurrence. -
Key words:
- Carcinoma of urinary bladder /
- MicroRNAs-15a /
- Recurrence /
- Muscular infiltration /
- Expression level
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表 1 miR-15a表达水平与膀胱癌临床特征的关系(例)
项目 例数 miR-15a表达水平 χ2值 P值 高表达(21例) 低表达(11例) 年龄(岁) ≤65 18 13 5 0.794 0.373 >65 14 8 6 性别 男性 19 14 5 1.347 0.246 女性 13 7 6 高血压 有 13 8 5 0.162 0.687 无 19 13 6 糖尿病 有 11 8 3 0.375 0.540 无 21 13 8 肌层浸润 NMIBC(Ta/T1) 21 18 3 10.929 0.001 MIBC(T2~T4) 11 3 8 远处转移 阴性 24 19 5 7.804 0.005 阳性 8 2 6 肿瘤分级 G1/G2 20 16 4 4.885 0.027 G3 12 5 7 表 2 多因素logistic回归分析miR-15a表达水平与膀胱肿瘤临床病理特征的关系
变量 B SE Wald χ2 P值 OR值 95% CI 远处转移(阳性) 3.165 1.536 4.248 0.039 23.693 1.168~480.580 肌层浸润(T2-T4) 3.152 1.355 5.410 0.020 23.375 1.642~332.757 肿瘤分级(G3) 3.191 1.509 4.473 0.034 24.304 1.264~467.480 注:变量赋值如下,远处转移阴性=0,阳性=1;肌层浸润NMIBC(Ta/T1)=0,MIBC(T2~T4)=1;肿瘤分级G1/G2=0,G3=1;miR-15a表达水平低表达=0,高表达=1。 -
[1] 李立强, 郭园园, 岳晓娥, 等. 二次等离子电切术在非肌层浸润性膀胱肿瘤中的应用[J]. 中华全科医学, 2020, 18(10): 1629-1632. https://www.cnki.com.cn/Article/CJFDTOTAL-SYQY202010005.htm [2] 李利军, 马志伟, 龚百生, 等. 吉西他滨在高危非肌层浸润性膀胱癌二次电切术后的应用[J]. 现代医药卫生, 2016, 32(16): 2560-2561. doi: 10.3969/j.issn.1009-5519.2016.16.045 [3] CORREIA DE SOUSA M, GJORGJIEVA M, DOLICKA D, et al. Deciphering miRNAs' action through miRNA editing[J]. Int J Mol Sci, 2019, 20(24): 6249. doi: 10.3390/ijms20246249 [4] KABEKKODU S P, SHUKLA V, VARGHESE V K, et al. Clustered miRNAs and their role in biological functions and diseases[J]. Biol Rev Camb Philos Soc, 2018, 93(4): 1955-1986. doi: 10.1111/brv.12428 [5] SALIMINEJAD K, KHORRAM KHORSHID H R, SOLEYMANI FARD S, et al. An overview of microRNAs: Biology, functions, therapeutics, and analysis methods[J]. J Cell Physiol, 2019, 234(5): 5451-5465. doi: 10.1002/jcp.27486 [6] JIN W, CHEN F, WANG K, et al. miR-15a/miR-16 cluster inhibits invasion of prostate cancer cells by suppressing TGF-β signaling pathway[J]. Biomed Pharmacother, 2018, 104: 637-644. doi: 10.1016/j.biopha.2018.05.041 [7] BRAGA T V, EVANGELISTA F C G, GOMES L C, et al. Evaluation of MiR-15a and MiR-16-1 as prognostic biomarkers in chronic lymphocytic leukemia[J]. Biomed Pharmacother, 2017, 92: 864-869. doi: 10.1016/j.biopha.2017.05.144 [8] GUO S, FESLER A, HUANG W, et al. Functional significance and therapeutic potential of mir-15a mimic in pancreatic ductal adenocarcinoma[J]. Mol Ther Nucleic Acids, 2020, 19: 228-239. doi: 10.1016/j.omtn.2019.11.010 [9] FAN B, CHEN L P, YUAN Y H, et al. MiR-15a-3p suppresses the growth and metastasis of ovarian cancer cell by targeting Twist1[J]. Eur Rev Med Pharmacol Sci, 2019, 23(5): 1934-1946. http://www.ncbi.nlm.nih.gov/pubmed/30915736 [10] ZHANG J, ZHAO H, GAO Y, et al. Secretory miRNAs as novel cancer biomarkers[J]. Biochim Biophys Acta, 2012, 1826(1): 32-43. http://www.onacademic.com/detail/journal_1000035027968610_315c.html [11] 肖文杰, 崔德威. MicroRNA-146与肿瘤[J]. 中国临床研究, 2015, 28(11): 1519-1520, 1524. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGCK201511039.htm [12] LIU D, ZHANG H, GE S, et al. Identification of HGF as a novel target of miR-15a/16/195 in gastric cancer[J]. Invest New Drugs, 2020, 38(4): 922-933. doi: 10.1007/s10637-019-00834-z [13] LI Q, WANG H, PENG H, et al. MicroRNAs: key players in bladder cancer[J]. Mol Diagn Ther, 2019, 23(5): 579-601. [14] TAHERI M, SHIRVANI-FARSANI Z, GHAFOURI-FARD S, et al. Expression profile of microRNAs in bladder cancer and their application as biomarkers[J]. Biomed Pharmacother, 2020, 131: 110703. doi: 10.1016/j.biopha.2020.110703 [15] JIA X, LIU H, XU C, et al. MiR-15a/16-1 deficiency induces IL-10-producing CD19 TIM-1 cells in tumor microenvironment[J]. J Cell Mol Med, 2019, 23(2): 1343-1353. doi: 10.1111/jcmm.14037 [16] LIU T, XU Z, OU D, et al. The miR-15a/16 gene cluster in human cancer: A systematic review[J]. J Cell Physiol, 2019, 234(5): 5496-5506. doi: 10.1002/jcp.27342 [17] WANG T, HOU J, LI Z, et al. MiR-15a-3p and miR-16-1-3p negatively regulate twist1 to repress gastric cancer cell invasion and metastasis[J]. Int J Biol Sci, 2017, 13(1): 122-134. doi: 10.7150/ijbs.14770 [18] LIU B, SUN T, WU G, et al. MiR-15a suppresses hepatocarcinoma cell migration and invasion by directly targeting[J]. Am J Transl Res, 2017, 9(2): 520-532. http://ajtr.org/files/ajtr0040269.pdf [19] ZIDAN H E, ABDUL-MAKSOUD R S, ELSAYED W S H, et al. Diagnostic and prognostic value of serum miR-15a and miR-16-1 expression among egyptian patients with prostate cancer[J]. IUBMB Life, 2018, 70(5): 437-444. doi: 10.1002/iub.1733 [20] CUI Y, YANG Y, REN L, et al. miR-15a-3p Suppresses prostate cancer cell proliferation and invasion by targeting SLC39A7 via downregulating Wnt/β-Catenin signaling pathway[J]. Cancer Biother Radiopharm, 2019, 34(7): 472-479. doi: 10.1089/cbr.2018.2722