博碩士論文 101293001 詳細資訊



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姓名 陳建隆(Chien-Lung Chen)  查詢紙本館藏   畢業系所 系統生物與生物資訊研究所
論文名稱 探索微型核糖核酸與慢性腎臟病及血液透析病人泌尿道上皮癌生物標記的相關性
(MicroRNA Profile is a Biomarker Associated with Urothelial Carcinoma in Chronic Kidney Disease and Hemodialysis Patients)
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摘要(中) 泌尿道上皮癌 (Urothelial Carcinoma, UC)為國人最常見的泌尿道腫瘤，它的發生率和復發率在慢性腎臟病和長期透析病人中更是高於一般人。目前泌尿道上皮癌的診斷以臨床症狀，影像學，細胞學及病理學為主，常因發現時間點較晚而耽誤病情，更無適當的腫瘤標記來協助診斷和治療，造成罹病率和死亡率都較高。微型核糖核酸(MicroRNAs, miRNAs) 已被證明是轉錄後基因表現的主要調節者，它可存在於組織、血液和尿液，與各種腎臟相關疾病及腫瘤有相關。自 2008 年開始便有以血液中微型核糖核酸做為生化標記的相關研究，我們實驗的目的為探索微型核糖核酸與泌尿道腫瘤生物標記相關性，並可應用於腫瘤的診斷、治療和追蹤。首先是以尿液及血液的檢體鑑別慢性腎臟病患者，罹患泌尿道上皮癌相關的 miRNAs 圖譜。利用微型 RNA 晶片 (miRNA array)篩選出 UC 相關之 miRNAs，經即時定量系統 (Quantitative real-time PCR array,
qPCR)的分析，透過驗證 (validation) 與測試 (testing)，在 250 組尿液檢體中，篩選出 4個 miRNAs 表現量的組合，ROC 可達 0.8211；再以 134 位病人合併尿液及血液檢體，篩選出 9 個 miRNAs 表現量的組合，ROC 為 0.8607。其中 miR-1274a 表現量更與 UC 的預後有顯著相關。其次是以血液檢體鑑別血液透析患者，罹患泌尿道上皮癌相關的
miRNAs 圖譜。，由 8 個血漿檢體篩選出 8 個候選的 miRNAs，再以 52 個檢體驗證，發現 5 個 miRNAs 表現量的組合，對於預測泌尿道上皮癌的 AUC 值為 0.882，敏感度為 80% (95% CI,0.5191 to 0.9567%)，專一度為 83.7% (95% CI, 0.6799 to 0.9381%)，這項診
斷工具對 9 個檢體進行測試實驗時，正確率更達 100%。另外也發現 miR-19b-1-5p 的表現量與 UC 的預後有相關性 (p=0.0382)。因此，我們發現 miRNAs 圖譜，具備了高於現有尿道上皮腫瘤標記的敏感度和專一度；更發現血漿 miR-19b-1-5p 及尿液 miR-1274a 與 UC 的預後具有顯著的相關性。未來本實驗結果將進一步，運用於預測、診斷、治療
和追蹤尿道上皮腫瘤。
摘要(英) Urothelial carcinoma (UC) is the most common urinary tract tumor among patients with chronic kidney disease (CKD) in Taiwan; this tumor is particularly prevalent among individuals on hemodialysis (HD). Urinalysis, image study, cytology, and cystoscopy are conventional screening methods and diagnostic tools for UC. However, urine cytology is characterized by poor sensitivity and specificity during the early stages of UC. Therefore, a non-invasive, inexpensive, and highly sensitive and specific UC biomarker is in urgent demand for improving UC screening, diagnosis, treatment, and follow-up. MiRNA is a small, non-coding RNA that is stable in the circulation and body fluids. It regulates epigenetically gene modification that is associated with kidney diseases and cancers. Therefore, we studied miRNAs as a novel ancillary diagnosis biomarker for detecting UC in CKD and HD patients. Firstly, we used urine and plasma miRNAs from CKD patients to develop ancillary biomarkers capable of detecting UC. A UC miRNA classifier composed of four urine miRNAs from 250 patients had an Receiver Operating Characteristics (ROC) of 0.8211; an additional nine miRNAs from the combination of urine and plasma samples from 134 CKD patients were detected with a ROC of 0.8607. In particular, the expression of urine miR-1247a was significantly different between CKD and UC patients and associated with the prognosis of UC. Secondly, we identified eight candidate miRNAs using a miRNA array and quantitative, real-time PCR (qPCR) from HD patients’ plasma. After validating and testing, the expression levels of miR-150-5p, miR-155-5p/miR-150-5p, miR-378a-3p/miR-150-5p, miR-636/miR-150-5p, miR-150-5p/ miR-210-3p, and miR-19b-1-5p/miR-378a-3p were significantly different between the UC and non-UC samples (p=0.035, 0.0048, 0.016, 0.024, 0.038, and 0.048, respectively). Meanwhile, we found that low miR-19b-1-5p expression was associated with a poorer UC prognosis (p=0.0382) based on Kaplan-Meier curve analysis. We used a miRNA classifier based on five miRNA expression levels to predict UC and found that the area under the curve (AUC) was 0.882, the sensitivity was 80% (95% CI, 0.5191–0.9567%), and the specificity was 83.7% (95% CI, 0.6799–0.9381%). We have determined novel urine and plasma miRNA classifiers that have higher sensitivity and specificity than existing UC biomarkers. Additionally, we found that plasma miR-19b-1-5p and urine miR-1247a had an association with UC prognosis. In the future, we will focus on miRNA classifiers as novel biomarkers for early detection, diagnosis, and treatment of UC.
關鍵字(中) ★ 泌尿道上皮癌
★ 微型核糖核酸
★ 慢性腎臟病
★ 血液透析		 關鍵字(英) ★ Urothelial carcinoma
★ MicroRNA
★ Chronic kidney disease
★ Hemodialysis
論文目次 Table of Contents
中文摘要 ................................................ i
Abstract ............................................... ii
誌謝 .................................................. iii
Table of Contents ...................................... iv
List of figures ........................................ vi
List of tales.......................................... vii
List of Abbreviations .......................... viii
Chapter 1 Introduction ................................ 1
1.1 Chronic Kidney Disease .............................. 1
1.2 Urothelial Carcino................................... 3
1.3 MicroRNAs ............................. 6
1.4 Motivation and Purpose ...................... 10
Chapter 2 Materials and Methods ........................ 11
2.1 Patient Recruitments ............................... 11
2.2 Preparation of Urine and Plasma..................... 11
2.3 RNA Extraction and Exogenous and Endogenous MiRNA controls ............................................... 12
2.4 The High Throughput Real-time Quantitative Reverse Transcriptase Polymerase Chain Reaction Analysis ....... 12
2.5 Survival Curve Analysis and Statistical Analysis.... 13
Chapter 3 Results ...................................... 14
3.1 Strategy for Screening Candidate UC biomarkers in CKD and HD Patients ........................................ 14
3.2 The 10 miRNAs are candidate UC biomarkers in CKD urine samples. ................... ............................16
3.3 MiRNAs Expression Linked to UC and Non-UC in CKD urine samples. ................ ...............................20
3.4 The Urine MiRNA Classifier to Predict UC in CKD Patients ................................................20
3.5 The 12 MiRNAs are Candidate UC Biomarkers in CKD Plasma Samples. ............. ..................................22
3.6 MiRNAs Expressions Linked to UC and non-UC in CKD plasma samples ............. ............................25
3.7 The Plasma MiRNA Classifier to Predict UC in CKD Patients ............................... ................25
3.8 Urine and Plasma MiRNA Classifiers to Predict UC in CKD patients ..................... ..........................27
3.9 Screen differentially expressed plasma miRNAs between UC and non-UC in HD patients ........................... 28
3.10 MiR-19b-1-5p Expression is Associated with UC Survival ........................................................ 35
3.11 The MiRNA Classifier Predicts UC in HD patients ... 37
Chapter 4 Discussion and Conclusions ................... 39
Chapter 5 Future Works ................................. 42
5.1 Examine the Prognosis Effects of MiRNAs that Associated with the Recurrence of UC in CKD and HD Patients....... 42
5.2 Validate the Newly Identified MiRNAs as Biomarkers Associated with UC Recurrence .......................... 43
5.3 Characterize Gene Targets and Functions of Newly Identified MiRNAs ...................................... 43
Bibliographies ......................................... 44
參考文獻 1. Foundation NK. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classifi cation, and stratifi cation. Am J Kidney Dis. 2002;39:S1–266.
2. Remuzzi G BA, Remuzzi A. Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Invest 2006;116:288–96.
3. Vassalotti JA SL, Levey AS. Testing for chronic kidney disease: a position statement from the National Kidney Foundation. Am J Kidney Dis 2007;50:169-80.
4. Stevens LA LA. Current status and future perspectives for CKD testing. Am J Kidney Dis 2009;53:S17–26.
5. Hsu CY OJ, Chertow GM, Fan D, McCulloch CE, Go AS. The risk of acute renal failure in patients with chronic kidney disease. Kidney Int 2008;74:101–07.
6. James MT HB, Wiebe N, et al. for the Alberta Kidney Disease Network. Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study. Lancet. 2010;376:2096–103.
7. Raman JD, Sosa RE, Vaughan Jr ED, Scherr DS. Pathologic features of bladder tumors after nephroureterectomy or segmental ureterectomy for upper urinary tract transitional cell carcinoma. Urology. 2007;69(2):251-4.
8. Matsui Y, Utsunomiya N, Ichioka K, Ueda N, Yoshimura K, Terai A, et al. Risk factors for subsequent development of bladder cancer after primary transitional cell carcinoma of the upper urinary tract. Urology. 2005;65(2):279-83.
9. Sexton WJ, Wiegand LR, Correa JJ, Politis C, Dickinson SI, Kang LC. Bladder cancer: a review of non-muscle invasive disease. Cancer control. 2010;17(4):256-68.
10. Lotan Y, Elias K, Svatek RS, Bagrodia A, Nuss G, Moran B, et al. Bladder cancer screening in a high risk asymptomatic population using a point of care urine based protein tumor marker. J Urol. 2009;182(1):52-7; discussion 8. doi: 10.1016/j.juro.2009.02.142. PubMed PMID: 19450825. 11. Ou J-H, C.-C. Pan, J. S.-N. Lin, T.-S. Tzai, W.-H. Yang, C.-C. Chang, H.-L. Cheng, Y.-M. Lin and Y.-C. Tong. Transitional Cell CTransitional Cell Carcinoma in Dialysis Patients. European urology. 2000;37(1):90-4.
12. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108. doi: 10.3322/caac.21262. PubMed PMID: 25651787.
13. WELFARE HPAMOHA. CANCER REGISTRY ANNUAL REPORT 2015 TAIWAN. 2017:611.
14. Wu M-J, Lian J-D, Yang C-R, Cheng C-H, Chen C-H, Lee W-C, et al. High cumulative incidence of urinary tract transitional cell carcinoma after kidney transplantation in Taiwan. American Journal of Kidney Diseases. 2004;43(6):1091-7. doi: 10.1053/j.ajkd.2004.03.016.
15. Chiang H, H. Guo, C. Hong, S. Lin and E. Lee. The incidence of bladder cancer in the black foot disease endemic area in Taiwan. New England Journal of Medicine. 1993;342(23):1686-92.
16. Gonwa TA, W. T. Corbett, H. M. Schey and V. M. Buckalew Analgesic-associated nephropathy and transitional cell carcinoma of the urinary tract. Annals of internal medicine. 1980;93(2):249-52.
17. Nortier JL, M.-C. M. Martinez, H. H. Schmeiser, V. M. Arlt, C. A. Bieler, M. Petein, M. F. Depierreux, L. De Pauw, D. Abramowicz and P. Urothelial carcinoma associated with the use of a Chinese herb (Aristolochia fangchi). New England Journal of Medicine. 2000;342(23):1686-92.
18. Lin MY, Kuo MC, Hung CC, Wu WJ, Chen LT, Yu ML, et al. Association of dialysis with the risks of cancers. PLoS One. 2015;10(4):e0122856.
19. Pu Y-S, Yang S-M, Huang Y-K, Chung C-J, Huang SK, Chiu AW-H, et al. Urinary arsenic profile affects the risk of urothelial carcinoma even at low arsenic exposure. Toxicology and applied pharmacology. 2007;218(2):99-106. 20. Chen C-H, Chiou H-Y, Hsueh Y-M, Chen C-J, Yu H-J, Pu Y-S. Clinicopathological characteristics and survival outcome of arsenic related bladder cancer in Taiwan. The Journal of urology. 2009;181(2):547-53.
21. Tracy TS, Kingston RL. Herbal products: toxicology and clinical pharmacology: Springer Science & Business Media; 2007.
22. Harling M, Schablon A, Schedlbauer G, Dulon M, Nienhaus A. Bladder cancer among hairdressers: a meta-analysis. Occupational and environmental medicine. 2010;67(5):351-8. 23. Chen C-H, Dickman KG, Huang C-Y, Shun C-T, Tai H-C, Huang K-H, et al. Recurrence pattern and TP53 mutation in upper urinary tract urothelial carcinoma. Oncotarget. 2016;7(29):45225.
24. Wu F, Wang T. Risk assessment of upper tract urothelial carcinoma related to aristolochic acid. Cancer Epidemiology and Prevention Biomarkers. 2013;22(5):81220.
25. Wong G, Staplin N, Emberson J, Baigent C, Turner R, Chalmers J, et al. Chronic kidney disease and the risk of cancer: an individual patient data meta-analysis of 32,057 participants from six prospective studies. BMC cancer. 2016;16(1):488.
26. van Rhijn BW, van der Poel HG, van der Kwast TH. Urine markers for bladder cancer surveillance: a systematic review. Eur Urol. 2005;47(6):736-48. doi: 10.1016/j.eururo.2005.03.014. PubMed PMID: 15925067.
27. Bialecki ES, Di Bisceglie AM. Diagnosis of hepatocellular carcinoma. Hpb. 2005;7(1):26-34.
28. Rauh-Hain JA, Krivak TC, del Carmen MG, Olawaiye AB. Ovarian cancer screening and early detection in the general population. Reviews in obstetrics and gynecology. 2011;4(1):15.
29. Goebell PJ, Groshen SL, Schmitz-Drager BJ. Guidelines for development of diagnostic markers in bladder cancer. World J Urol. 2008;26(1):5-11. doi: 10.1007/s00345-008-0240-9. PubMed PMID: 18253738.
30. Shahrokh F. Shariat EIC, Michael W. Kattan, , Slawin KM. Beyond prostate-specific antigen new serologic biomarkers for improved diagnosis and management of prostate cancer. Rev Urol 2004;6:58-72.
31. Steiner H, Bergmeister M, Verdorfer I, Granig T, Mikuz G, Bartsch G, et al. Early results of bladder-cancer screening in a high-risk population of heavy smokers. BJU Int. 2008;102(3):291-6. doi: 10.1111/j.1464-410X.2008.07596.x. PubMed PMID: 18336612.
32. Schmitz-Drager BJ, Tirsar LA, Schmitz-Drager C, Dorsam J, Mellan Z, Bismarck E, et al. Immunocytology in the assessment of patients with asymptomatic hematuria. World J Urol. 2008;26(1):31-7. doi: 10.1007/s00345-007-0228-x. PubMed PMID: 18075743.
33. Mowatt G, Zhu S, Kilonzo M, Boachie C, Fraser C, Griffiths TRL, et al. Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer. Health Technology Assessment. 2010;14(4). doi: 10.3310/hta14040.
34. Winter J, Jung S, Keller S, Gregory RI, Diederichs S. Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol. 2009;11(3):22834. doi: 10.1038/ncb0309-228. PubMed PMID: 19255566.
35. Yu Y, Bai F, Qin N, Liu W, Sun Q, Zhou Y, et al. Non-Proximal Renal Tubule-Derived Urinary Exosomal miR-200b as a Biomarker of Renal Fibrosis. Nephron. 2018;139(3):269-82. doi: 10.1159/000487104. PubMed PMID: 29539618.
36. Lee RC, R.L. Feinbaum, and V. Ambros. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. cell. 1993;75(5):84354.
37. Han J, et al. The Drosha-DGCR8 complex in primary microRNA processing. Genes Dev. 2004;18(24):3016-27.
38. Yi R, et al. Exportin-5 mediates the nuclear export of pre-microRNAs and short hairpin RNAs. Genes Dev. 2003;17(24):3011-6.
39. Bernstein E, et al. Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001;409(6818):363-6.
40. Hammond SM, et al. An RNA-directed nuclease mediates post-transcriptional gene silencing in Drosophila cells. nature. 2000;404(6775):293-6.
41. Doench JGaPA. Sharp, Specificity of microRNA target selection in translational repression. . Genes Dev. 2004;18(5):504-11.
42. Lewis BP, C.B. Burge, and D.P. Bartel. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. cell. 2005;120(1):15-20.
43. He LaGJH. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5(7):522-31.
44. Zhang WaHTL. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 2002;12(1):9-18.
45. Waltraud X Schulze LD, and Matthias Mann. Phosphotyrosine interactome of the ErbB-receptor kinase family. Mol Syst Biol. 2005;1:2005 0008.
46. Gray SV, et. al. Melanoma biology and new targeted therapy. Nature. 2007;445(7130): 851-7.
47. Montagut CaJS. Targeting the RAF-MEK-ERK pathway in cancer therapy. Cancer Lett. 2009;283(2):125-34.
48. Calin GA, Croce CM. MicroRNA-cancer connection: the beginning of a new tale. Cancer Res. 2006;66(15):7390-4. doi: 10.1158/0008-5472.CAN-06-0800. PubMed PMID: 16885332. 49. Izzotti A, Larghero P, Longobardi M, Cartiglia C, Camoirano A, Steele VE, et al. Dose-responsiveness and persistence of microRNA expression alterations induced by cigarette smoke in mouse lung. Mutat Res. 2011;717(1-2):9-16. doi: 10.1016/j.mrfmmm.2010.12.008. PubMed PMID: 21185844.
50. Farazi TA, Hoell JI, Morozov P, Tuschl T. MicroRNAs in human cancer. Adv Exp Med Biol. 2013;774:1-20. doi: 10.1007/978-94-007-5590-1_1. PubMed PMID: 23377965; PubMed Central PMCID: PMCPMC3704221.
51. Xuelian Li YS, Zhihua Yin, Xiaoxia Xue and Baosen Zhou. An eight-miRNA signature as a potential biomarker for predicting survival in lung adenocarcinoma. Journal of Translational medicine. 2014;12:159.
52. Filipowicz W BS, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9:102-14.
53. O H. Gene regulation by transcription factors and microRNAs. Science. 2008;319:1785-6.
54. Kong YW F-MD, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol 2012;13(6):e249-58.
55. Lin Zhang JH, Nuo Yang, Joel Greshock, Molly S. Megraw, Antonis Giannakakis, Shun Liang, Tara L. Naylor, Andrea Barchetti, Michelle R. Ward, George Yao, Angelica Medina, Ann O’Brien-Jenkins, Dionyssios Katsaros, Artemis Hatzigeorgiou, Phyllis A. Gimotty, Barbara L. Weber, and George Coukos. microRNAs exhibit high frequency genomic alterations in human cancer. Proceedings of the National Academy of Sciences. 2006;103(24):9136-41.
56. Zhang Y YP, Wang XF. Microenvironmental regulation of cancer metastasis by miRNAs. Trends Cell Biol. 2014;24(3):153-60.
57. Nakamura K SK, Yoshimura A, Kinose Y, Nakatsuka E, Kimura T. Clinical relevance of circulating cell-free microRNAs in ovarian cancer. Mol Cancer. 2016;15(1):48.
58. Mall C, Rocke DM, Durbin-Johnson B, Weiss RH. Stability of miRNA in human urine supports its biomarker potential. Biomark Med. 2013;7(4):623-31. doi: 10.2217/bmm.13.44. PubMed PMID: 23905899; PubMed Central PMCID: PMCPMC3885156.
59. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513-8. doi: 10.1073/pnas.0804549105. PubMed PMID: 18663219; PubMed Central PMCID: PMCPMC2492472.
60. Wanfen Zhang CZ, Huimei Chen, Limin Li, Yuanmao Tu, Chunbei Liu, Shaolin Shi, Ke Zen, and, Liu Z. Evaluation of microRNAs miR-196a, miR-30a-5P, and miR-490 as biomarkers of disease activity among patients with FSGS. Clin J Am Soc Nephrol. 2014;9(9):1545-52.
61. Kosaka N, Iguchi H, Ochiya T. Circulating microRNA in body fluid: a new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010;101(10):2087-92. doi: 10.1111/j.1349-7006.2010.01650.x. PubMed PMID: 20624164. 62. Shlomit Gilad. EM, Yariv Yogev, Sima Benjamin, Danit Lebanony, Noga Yerushalmi, Hila Benjamin, Michal Kushnir, Hila Cholakh, Nir Melamed, Zvi Bentwich, Moshe Hod, Yaron Goren, Ayelet Chajut. Serum MicroRNAs Are Promising Novel Biomarkers. PLoS One. 2008;3(9):e3148.
63. Lu J GG, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR. MicroRNA expression profiles classify human cancers. nature. 2005;435(7043): 8348.
64. Rosenfeld N AR, Meiri E, Rosenwald S, Spector Y, Zepeniuk M, Benjamin H, Shabes N, Tabak S, Levy A, Lebanony D, Goren Y, Silberschein E, Targan N, Ben-Ari A, Gilad S, Sion-Vardy N, Tobar A, Feinmesser M, Kharenko O, Nativ O, Nass D, Perelman M, Yosepovich A, Shalmon B, Polak-Charcon S, Fridman E, Avniel A, Bentwich I, Bentwich Z, Cohen D, Chajut A, Barshack I. MicroRNAs accurately identify cancer tissue origin. Nat Biotechnol. 2008;26(4):462-9.
65. DP B. MicroRNAs: target recognition and regulatory functions. cell. 2009;136(2):215-33.
66. Turchinovich A WL, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Research. 2012;39(16):7223-33.
67. Wang WT ZY, Han BW, Hong SJ, Chen YQ. Circulating microRNAs identified in a genome-wide serum microRNA expression analysis as noninvasive biomarkers for endometriosis. J Clin Endocrinol Metab. 2013;98(1):281-9. 68. Etheridge A LI, Hood L, Galas D, Wang K. Extracellular microRNA: a new source of biomarkers. Mutat Res. 2011;717(1-2):85-90.
69. Dong F XT, Shen Y, Zhong S, Chen S, Ding Q1, Shen Z. Dysregulation of miRNAs in bladder cancer altered expression with aberrant biogenesis procedure. Oncotarget. 2017;8(16):27547-68. 70. Enokida H, Yoshino H, Matsushita R, Nakagawa M. The role of microRNAs in bladder cancer. Investig Clin Urol. 2016;57 Suppl 1:S60-76. doi: 10.4111/icu.2016.57.S1.S60. PubMed PMID: 27326409; PubMed Central PMCID: PMCPMC4910767. 71. Homami A GF. MicroRNAs as biomarkers associated with bladder cancer. Med J Islam Repub Iran. 2016;30:475. 72. Jung M SA, Steiner I, Kempkensteffen C, Stephan C, Erbersdobler A, Jung K. Robust microRNA stability in degraded RNA preparations from human tissue and cell samples. Clin Chem. 2010;56(6):998-1006. 73. I-Fang Chung S-JC, Chen-Yang Chen, Shu-Hsuan Liu, Chia-Yang Li, Chia-Hao Chan, Chuan-Chi Shih and Wei-Chung Cheng. YM500v3: a database for small RNA sequencing in human cancer research. Nucleic Acids Research. 2017;45:925-31. 74. Gilad S, Meiri E, Yogev Y, Benjamin S, Lebanony D, Yerushalmi N, et al. Serum microRNAs are promising novel biomarkers. PLoS One. 2008;3(9):e3148. Epub 2008/09/06. doi: 10.1371/journal.pone.0003148. PubMed PMID: 18773077; PubMed Central PMCID: PMC2519789.
75. Peng Y DW, Lin TX, Zhong GZ, Liao B, Wang B, et al. MicroRNA-155 promotes bladder cancer growth by repressing the tumor suppressor DMTF1. Oncotarget. 2015;6:16043-58. 76. Friedman JM, Liang G, Liu CC, Wolff EM, Tsai YC, Ye W, et al. The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer research. 2009;69(6):2623-9. Epub 2009/03/05. doi: 10.1158/0008-5472.CAN-08-3114. PubMed PMID: 19258506.
77. Lei Y, Hu X, Li B, Peng M, Tong S, Zu X, et al. miR-150 modulates cisplatin chemosensitivity and invasiveness of muscle-invasive bladder cancer cells via targeting PDCD4 in vitro. Medical science monitor : international medical journal of experimental and clinical research. 2014;20:1850-7. Epub 2014/10/08. doi: 10.12659/MSM.891340. PubMed PMID: 25287716; PubMed Central PMCID: PMCPMC4199406. 78. Ma Y, Zhang P, Wang F, Zhang H, Yang J, Peng J, et al. miR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancer.Gut. 2012;61(10):1447-53. Epub 2011/11/05. doi: 10.1136/gutjnl-2011-301122. PubMed PMID: 22052060.
79. Motawi TK, Rizk SM, Ibrahim TM, Ibrahim IA. Circulating microRNAs, miR-92a, miR-100 and miR-143, as non-invasive biomarkers for bladder cancer diagnosis. Cell biochemistry and function. 2016;34(3):142-8. Epub 2016/02/27. doi: 10.1002/cbf.3171. PubMed PMID: 26916216.
80. Allegra A, Alonci A, Campo S, Penna G, Petrungaro A, Gerace D, et al. Circulating microRNAs: new biomarkers in diagnosis, prognosis and treatment of cancer (review). Int J Oncol. 2012;41:1897-912.
81. Tolle A, Jung M, Rabenhorst S, Kilic E, Jung K, Weikert S. Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer. Oncology reports. 2013;30(4):1949-56. Epub 2013/07/24. doi: 10.3892/or.2013.2621. PubMed PMID: 23877086.
82. Jiang X, Du L, Wang L, Li J, Liu Y, Zheng G, et al. Serum microRNA expression signatures identified from genome-wide microRNA profiling serve as novel noninvasive biomarkers for diagnosis and recurrence of bladder cancer. International journal of cancer. 2015;136(4):854-62. Epub 2014/06/26. doi: 10.1002/ijc.29041. PubMed PMID: 24961907. 83. Fang Z, Dai W, Wang X, Chen W, Shen C, Ye G, et al. Circulating miR-205: a promising biomarker for the detection and prognosis evaluation of bladder cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016;37(6):8075-82. Epub 2015/12/31. doi: 10.1007/s13277015-4698-y. PubMed PMID: 26715266.
84. Du M, Shi D, Yuan L, Li P, Chu H, Qin C, et al. Circulating miR-497 and miR-663b in plasma are potential novel biomarkers for bladder cancer. Scientific reports. 2015;5:10437. Epub 2015/05/28. doi: 10.1038/srep10437. PubMed PMID: 26014226; PubMed Central PMCID: PMCPMC4444850.
指導教授 洪炯宗 馬念涵(Jorng-Tzong Horng Nianhan Ma) 審核日期 2019-6-19
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