Diagnostic Pathology | |
Prognostic value of miR-96 in patients with acute myeloid leukemia | |
Yun-xian Chen3  Jianguo Fu2  Junfeng Zhu4  Quanyi Lu1  Jiangning Zhao1  | |
[1] Department of Hematology, Zhongshan Hospital of Xiamen University, 361004 Xiamen, Fujian, China;Department of Nosocomial Infection Control Department, Zhongshan Hospital of Xiamen University, 361004 Xiamen, Fujian, China;Department of Hematology, the First Affiliated Hospital of Sun Yat-Sen University, 510080 Guangzhou, Guangdong, China;Department of Pathology, the First Affiliated Hospital of Sun Yat-Sen University, 510080 Guangzhou, Guangdong, China | |
关键词: Prognosis; Real-time quantitative RT-PCR assay; Acute myeloid leukemia; miR-96; | |
Others : 802007 DOI : 10.1186/1746-1596-9-76 |
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received in 2014-01-28, accepted in 2014-03-18, 发布年份 2014 | |
【 摘 要 】
Objective
Aberrant expression of miRNA (miR)-96 is associated with tumorigenesis and tumor progression in several solid cancers. However, little is known about the expression and prognostic value of miR-96 in acute myeloid leukemia (AML). Therefore, the aim of this study was to investigate the correlation of miR-96 expression with clinicopathological features and prognosis of AML.
Methods
Real-time quantitative RT-PCR assay was performed to evaluate the expression levels of miR-96 in mononuclear cells from bone marrow or peripheral blood specimens in 86 patients with newly diagnosed AML.
Results
Compared with normal controls, miR-96 expression was significantly downregulated in patients with newly diagnosed AML (P < 0.001). In analysis of 14 diagnosis/CR-paired samples, the expression level of miR-96 was found markedly elevated in patients after treatment than before (P < 0.001). Moreover, lower levels of miR-96 were associated with a higher white blood cell count, bone marrow blast count (P < 0.001 and 0.022, respectively), and lower hemoglobin and platelet count (P = 0.036 and 0.033, respectively). Although the low-expression group seemed to have a lower CR rate (53.85% vs 70.0%), there was no significant difference between the two groups (P = 0.213). The low-expression group had a lower relapse-free survival (RFS) (P = 0.038) and overall survival (OS) (P = 0.022) compared with the high-expression group during a median follow-up of 20 months.
Conclusion
Our data demonstrated that the expression of miR-96 was downregulated in newly diagnosed AML patients and associated with leukemic burden, as well as RFS and OS. This suggests that miR-96 detection might become a potential biomarker of prognosis and monitoring in AML.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1434808553949498 webcite
【 授权许可】
2014 Zhao et al.; licensee BioMed Central Ltd.
【 预 览 】
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20140708014519465.pdf | 455KB | download | |
Figure 3. | 43KB | Image | download |
Figure 2. | 66KB | Image | download |
Figure 1. | 42KB | Image | download |
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【 参考文献 】
- [1]Tallman MS, Gilliland DG, Rowe JM: Drug therapy for acute myeloid leukemia. Blood 2005, 106:1154-1163.
- [2]Garzon R, Volinia S, Liu CG, Fernandez-Cymering C, Palumbo T, Pichiorri F, Fabbri M, Coombes K, Alder H, Nakamura T, Flomenberg N, Marcucci G, Calin GA, Kornbalu SM, Kantarjian H, Bloomfield CD, Andreeff M, Croce CM: MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia. Blood 2008, 111:3183-3189.
- [3]Jongen-Lavrencic M, Sun SM, Dijkstra MK, Valk PJ, Lowenberg B: MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia. Blood 2008, 111:5078-5085.
- [4]Dixon-McIver A, East P, Mein CA, Cazier JB, Molloy G, Chaplin T, Andrew Lister T, Young BD, Debernardi S: Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia. PLoS One 2008, 3:e2141.
- [5]Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004, 116:281-297.
- [6]Chen T: The role of MicroRNA in chemical carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2010, 28:89-124.
- [7]Ufkin ML, Peterson S, Yang X, Driscoll H, Duarte C, Sathyanarayana P: miR-125a regulates cell cycle, proliferation, and apoptosis by targeting the ErbB pathway in acute myeloid leukemia. Leuk Res 2014, 38:402-410.
- [8]Wang XS, Gong JN, Yu J, Wang F, Zhang XH, Yin XL, Tan ZQ, Luo ZM, Yang GH, Shen C, Zhang JW: MicroRNA-29a and microRNA-142-3p are regulators of myeloid differentiation and acute myeloid leukemia. Blood 2012, 119:4992-5004.
- [9]Zhu J, Feng Y, Ke Z, Yang Z, Zhou J, Huang X, Wang L: Down-regulation of miR-183 promotes migration and invasion of osteosarcoma by targeting Ezrin. Am J Pathol 2012, 180:2440-2451.
- [10]He T, Qi F, Jia L, Wang S, Song N, Guo L, Fu Y, Luo Y: MicroRNA-542-3p inhibits tumor angiogenesis by targeting Angiopoietin2. J Pathol 2014. [Epub ahead of print]
- [11]Wang W, Li F, Zhang Y, Tu Y, Yang Q, Gao X: Reduced expression of miR-22 in gastric cancer is related to clinicopathologic characteristics or patient prognosis. Diagn Pathol 2013, 8:102. BioMed Central Full Text
- [12]Marcucci G, Maharry K, Radmacher MD, Mrozek K, Vukosavljevic T, Paschka P, Whitman SP, Langer C, Baldus CD, Liu CG, Ruppert AS, Powell BL, Carroll AJ, Caliqiuri MA, Kolitz JE, Larson RA, Bloomfield CD: Prognostic significance of, and gene and microRNA expression signatures associated with, CEBPA mutations in cytogenetically normal acute myeloid leukemia with high-risk molecular features: a cancer and leukemia group B study. J Clin Oncol 2008, 26:5078-5087.
- [13]Li G, Zhang Z, Tu Y, Jin T, Liang H, Cui G, He S, Gao G: Correlation of microRNA-372 upregulation with poor prognosis in human glioma. Diagn Pathol 2013, 8:1. BioMed Central Full Text
- [14]Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, Miller K, Lein M, Kristiansen G, Jung K: Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma. Int J Cancer 2010, 126:1166-1176.
- [15]Lu J, Getz G, 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, 435:834-838.
- [16]Haflidadóttir BS, Larne O, Martin M, Persson M, Edsjö A, Bjartell A, Ceder Y: Upregulation of miR-96 enhances cellular proliferation of prostate cancer cells through FOXO1. PLoS One 2013, 8:e72400.
- [17]Yamada Y, Enokida H, Kojima S, Kawakami K, Chiyomaru T, Tatarano S, Yoshino H, Kawahara K, Nishiyama K, Seki N, Nakagawa M: MiR-96 and miR-183 detection in urine serve as potential tumor markers of urothelial carcinoma: correlation with stage and grade, and comparison with urinary cytology. Cancer Sci 2011, 102:522-529.
- [18]Wang Y, Luo H, Li Y, Chen T, Wu S: Yang L: hsa-miR-96 up-regulates MAP4K1 and IRS1 and may function as a promising diagnostic marker in human bladder urothelial carcinomas. Mol Med Rep 2012, 5:260-265.
- [19]Xu D, He X, Chang Y, Xu C, Jiang X, Sun S, Lin J: Inhibition of miR-96 expression reduces cell proliferation and clonogenicity of HepG2 hepatoma cells. Oncol Rep 2013, 29:653-661.
- [20]Lin H, Dai T, Xiong H, Zhao X, Chen X, Yu C, Li J, Wang X, Song L: Unregulated miR-96 induces cell proliferation in human breast cancer by downregulating transcriptional factor FOXO3a. PLoS One 2010, 5:e15797.
- [21]Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD: Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol 2003, 21:4642-4649.
- [22]Schmittgen TD, Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc 2008, 3:1101-1108.
- [23]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 2001, 25:402-408.
- [24]De Mello MR1, Albuquerque DM, Pereira-Cunha FG, Albanez KB, Pagnano KB, Costa FF, Metze K, Lorand-Metze I: Molecular characteristics and chromatin texture features in acute promyelocytic leukemia. Diagn Pathol 2012, 7:75. BioMed Central Full Text
- [25]Masetti R, Togni M, Astolfi A, Pigazzi M, Manara E, Indio V, Rizzari C, Rutella S, Basso G, Pession A, Locatelli F: DHH-RHEBL1 fusion transcript: a novel recurrent feature in the new landscape of pediatric CBFA2T3-GLIS2-positive acute myeloid leukemia. Oncotarget 2013, 4:1712-1720.
- [26]Masetti R, Pigazzi M, Togni M, Astolfi A, Indio V, Manara E, Casadio R, Pession A, Basso G, Locatelli F: CBFA2T3-GLIS2 fusion transcript is a novel common feature in pediatric, cytogenetically normal AML, not restricted to FAB M7 subtype. Blood 2013, 121:3469-3472.
- [27]Kralik JM1, Kranewitter W, Boesmueller H, Marschon R, Tschurtschenthaler G, Rumpold H, Wiesinger K, Erdel M, Petzer AL, Webersinke G: Characterization of a newly identified ETV6-NTRK3 fusion transcript in acute myeloid leukemia. Diagn Pathol 2011, 6:19. BioMed Central Full Text
- [28]Sánchez‒Espiridión B, Martín‒Moreno AM, Montalbán C, Figueroa V, Vega F, Younes A, Medeiros LJ, Alvés FJ, Canales M, Estévez M: MicroRNA signatures and treatment response in patients with advanced classical Hodgkin lymphoma. Br J Haematol 2013, 162:336-347.
- [29]Mihelich BL, Khramtsova EA, Arva N, Vaishnav A, Johnson DN, Giangreco AA, Martens-Uzunova E, Bagasra O, Kajdacsy-Balla A, Nonn L: miR-183-96-182 cluster is overexpressed in prostate tissue and regulates zinc homeostasis in prostate cells. J Biol Chem 2011, 286:44503-44511.
- [30]Tang H, Bian Y, Tu C, Wang Z, Yu Z, Liu Q, Xu G, Wu M, Li G: The miR-183/96/182 cluster regulates oxidative apoptosis and sensitizes cells to chemotherapy in gliomas. Curr Cancer Drug Targets 2013, 13:221-231.
- [31]Weeraratne SD, Amani V, Teider N, Pierre-Francois J, Winter D, Kye MJ, Sengupta S, Archer T, Remke M, Bai AH, Warren P, Pfister SM, Steen JA, Pomeroy SL, Cho YJ: Pleiotropic effects of miR-183 96 182 converge to regulate cell survival, proliferation and migration in medulloblastoma. Acta Neuropathol 2012, 123:539-552.
- [32]Chen RX, Xia YH, Xue TC, Ye SL: Suppression of microRNA-96 expression inhibits the invasion of hepatocellular carcinoma cells. Mol Med Rep 2012, 5:800-804.
- [33]Yu S, Lu Z, Liu C, Meng Y, Ma Y, Zhao W, Liu J, Yu J, Chen J: miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer. Cancer Res 2010, 70:6015-6025.
- [34]Vishwamitra D, Li Y, Wilson D, Manshouri R, Curry CV, Shi B, Tang XM, Sheehan AM, Wistuba II, Shi P, Amin HM: MicroRNA 96 is a post-transcriptional suppressor of anaplastic lymphoma kinase expression. Am J Pathol 2012, 180:1772-1780.1.