The expression of microRNA-375 in plasma and tissue is matched in human colorectal cancer

BMC Cancer

Lingling Xu²  Minzhe Li¹  Min Wang²  Dong Yan²  Guosheng Feng¹  Guangyu An² 

[1] Department of Surgery, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China

[2] Department of Oncology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China

关键词: Diagnosis;    Biomarker;    Tissue;    Plasma;    MicroRNA;    Colorectal cancer;   

Others  :  1121026
DOI  :  10.1186/1471-2407-14-714

 received in 2014-05-10, accepted in 2014-09-22,  发布年份 2014

【 摘 要 】

Background

MicroRNAs (miRNAs) offer great potential as cancer biomarkers. The importance of miRNAs profiling in tissue and body fluids in colorectal cancer (CRC) have been addressed respectively in many studies. The purpose of our study is to systematically assess the expression of miRNAs in cancer tissue and matched plasma samples and to evaluate their usefulness as minimally invasive diagnostic biomarkers for the detection of CRC.

Methods

The study was divided into two phases: firstly, qRT-PCR based TaqMan Low Density MiRNA Arrays (TLDAs) was used to screen the differentially expressed miRNAs in 6 plasma samples of CRC patients and 6 healthy controls. Secondly, marker validation by stem-loop reverse transcription real-time PCR using an independent set of paired cancer tissues (n = 88) and matched plasma samples (CRC, n = 88; control, n = 40). Correlation analysis was determined by Pearson’s test. Receiver operating characteristic curve analyses were applied to obtain diagnostic utility of the differentially expressed miRNAs. Target gene prediction and signal pathway analyses were used to predict the function of miRNAs.

Results

TLDAs identified 42 miRNAs, which were differentially expressed in patients and healthy individuals. Five of them (miR-375, miR-150, miR-206, miR-125b and miR-126*) were chosen to be validated in plasma and tissue samples. The results indicated that for plasma sample, miR-375 (p < 0.0001) and miR-206 (p = 0.0002) were dysregulated and could discriminate CRC patients from healthy controls. For tissue samples, miR-375 (p < 0.0001), miR-150 (p < 0.0001), miR-125b (p = 0.0065) and miR-126*(p = 0.0009) were down-regulated. miR-375 was significantly down-regulated and positively correlated in both tissue and plasma samples (r = 0.4663, p = 0.0007). Gene ontology and signal pathway analyses showed that most of the target genes that were regulated by miR-375 were involved in some critical pathways in the development and progression of cancer.

Conclusions

Our results indicate that the down-regulation of miR-375 in plasma and tissue is matched in CRC. Moreover, bioinformatics prediction revealed miR-375 association with some critical signal pathways in the development and progression of CRC. Therefore, plasma miR-375 holds great promise to be an alternative tissue biomarker for CRC detection.

【 授权许可】

   
2014 Xu et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Siegel R, Desantis C, Jemal A: Colorectal cancer statistics. CA Cancer J Clin 2014, 64:104-117.
• [2]Goh LY, Leow AH, Goh KL: Observations on the epidemiology of gastrointestinal and liver cancers in the Asian-Pacific region. J Dig Dis 2014. in press
• [3]Soerjomataram I, Thong MS, Ezzati M, Lamont EB, Nusselder WJ, van de Poll-Franse LV: Most colorectal cancer survivors live a large proportion of their remaining life in good health. Cancer Causes Control 2012, 23:1421-1428.
• [4]Bosch LJ, Carvalho B, Fijneman RJ, Jimenez CR, Pinedo HM, van Engeland M, Meijer GA: Molecular tests for colorectal cancer screening. Clin Colorectal Cancer 2011, 10:8-23.
• [5]Senore C, Ederle A, Fantin A, Andreoni B, Bisanti L, Grazzini G, Zappa M, Ferrero F, Marutti A, Giuliani O, Armaroli P, Segnan N: Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting. J Med Screen 2011, 18:128-134.
• [6]Khalid-de Bakker CA, Jonkers DM, Sanduleanu S, de Bruine AP, Meijer GA, Janssen JB, van Engeland M, Stockbrugger RW, Masclee AA: Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas. Canc Prev Res (Phila) 2011, 4:1563-1571.
• [7]Lee YS, Dutta A: MicroRNAs in cancer. Annu Rev Pathol 2009, 4:199-227.
• [8]Babashah S, Soleimani M: The oncogenic and tumour suppressive roles of microRNAs in cancer and apoptosis. Eur J Cancer 2011, 47:1127-1137.
• [9]He L, Hannon GJ: MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 2004, 5:522-531.
• [10]Ahmed FE, Ahmed NC, Vos PW, Bonnerup C, Atkins JN, Casey M, Nuovo GJ, Naziri W, Wiley JE, Mota H, Allison RR: Diagnostic microRNA markers to screen for sporadic human colon cancer in stool: I. Proof of principle. Cancer Genomics Proteomics 2013, 10:93-113.
• [11]Salendo J, Spitzner M, Kramer F, Zhang X, Jo P, Wolff HA, Kitz J, Kaulfuss S, Beissbarth T, Dobbelstein M, Ghadimi M, Grade M, Gaedcke J: Identification of a microRNA expression signature for chemoradiosensitivity of colorectal cancer cells, involving miRNAs-320a, -224, -132 and let7g. Radiother Oncol 2013, 108:451-457.
• [12]Zhang GJ, Zhou H, Xiao HX, Li Y, Zhou T: MiR-378 is an independent prognostic factor and inhibits cell growth and invasion in colorectal cancer. BMC Cancer 2014, 14:109. BioMed Central Full Text
• [13]Liu Y, Zhou Y, Feng X, Yang P, Yang J, An P, Wang H, Ye S, Yu C, He Y, Luo H: Low expression of microRNA-126 is associated with poor prognosis in colorectal cancer. Genes Chromosomes Cancer 2014, 53:358-365.
• [14]Vickers MM, Bar J, Gorn-Hondermann I, Yarom N, Daneshmand M, Hanson JE, Addison CL, Asmis TR, Jonker DJ, Maroun J, Lorimer IA, Goss GD, Dimitroulakos J: Stage-dependent differential expression of microRNAs in colorectal cancer: potential role as markers of metastatic disease. Clin Exp Metastasis 2012, 29:123-132.
• [15]Zhang JX, Song W, Chen ZH, Wei JH, Liao YJ, Lei J, Hu M, Chen GZ, Liao B, Lu J, Zhao HW, Chen W, He YL, Wang HY, Xie D, Luo JH: Prognostic and predictive value of a microRNA signature in stage II colon cancer: a microRNA expression analysis. Lancet Oncol 2013, 14:1295-1306.
• [16]Wang CJ, Zhou ZG, Wang L, Yang L, Zhou B, Gu J, Chen HY, Sun XF: Clinicopathological significance of microRNA-31, -143 and -145 expression in colorectal cancer. Dis Markers 2009, 26:27-34.
• [17]Schee K, Boye K, Abrahamsen TW, Fodstad O, Flatmark K: Clinical relevance of microRNA miR-21, miR-31, miR-92a, miR-101, miR-106a and miR-145 in colorectal cancer. BMC Cancer 2012, 12:505. BioMed Central Full Text
• [18]Ng EK, Chong WW, Jin H, Lam EK, Shin VY, Yu J, Poon TC, Ng SS, Sung JJ: Differential expression of microRNAs in plasma of patients with colorectal cancer: a potential marker for colorectal cancer screening. Gut 2009, 58:1375-1381.
• [19]Zanutto S, Pizzamiglio S, Ghilotti M, Bertan C, Ravagnani F, Perrone F, Leo E, Pilotti S, Verderio P, Gariboldi M, Pierotti MA: Circulating miR-378 in plasma: a reliable, haemolysis-independent biomarker for colorectal cancer. Br J Cancer 2014, 110:1001-1007.
• [20]Irizarry RA, Hobbs B, Collin F, Beazer-Barclay YD, Antonellis KJ, Scherf U, Speed TP: Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics 2003, 4:249-264.
• [21]Elzagheid A, Buhmeida A, Korkeila E, Collan Y, Syrjanen K, Pyrhonen S: Nuclear beta-catenin expression as a prognostic factor in advanced colorectal carcinoma. World J Gastroenterol 2008, 14:3866-3871.
• [22]Luo X, Stock C, Burwinkel B, Brenner H: Identification and evaluation of plasma microRNAs for early detection of colorectal cancer. PLoS One 2013, 8:e62880.
• [23]Ma Y, Zhang P, Wang F, Zhang H, Yang J, Peng J, Liu W, Qin H: miR-150 as a potential biomarker associated with prognosis and therapeutic outcome in colorectal cancer. Gut 2012, 61:1447-1453.
• [24]Cao M, Hou D, Liang H, Gong F, Wang Y, Yan X, Jiang X, Wang C, Zhang J, Zen K, Zhang CY, Chen X: miR-150 promotes the proliferation and migration of lung cancer cells by targeting SRC kinase signalling inhibitor 1. Eur J Cancer 2014, 50:1013-1024.
• [25]Yokobori T, Suzuki S, Tanaka N, Inose T, Sohda M, Sano A, Sakai M, Nakajima M, Miyazaki T, Kato H, Kuwano H: MiR-150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducer ZEB1. Cancer Sci 2013, 104:48-54.
• [26]Srivastava SK, Bhardwaj A, Singh S, Arora S, Wang B, Grizzle WE, Singh AP: MicroRNA-150 directly targets MUC4 and suppresses growth and malignant behavior of pancreatic cancer cells. Carcinogenesis 2011, 32:1832-1839.
• [27]Huang S, Chen Y, Wu W, Ouyang N, Chen J, Li H, Liu X, Su F, Lin L, Yao Y: miR-150 promotes human breast cancer growth and malignant behavior by targeting the pro-apoptotic purinergic P2X7 receptor. PLoS One 2013, 8:e80707.
• [28]Rasio D, Negrini M, Manenti G, Dragani TA, Croce CM: Loss of heterozygosity at chromosome 11q in lung adenocarcinoma: identification of three independent regions. Cancer Res 1995, 55:3988-3991.
• [29]Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Menard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM: MicroRNA gene expression deregulation in human breast cancer. Cancer Res 2005, 65:7065-7070.
• [30]Ak S, Tunca B, Tezcan G, Cecener G, Egeli U, Yilmazlar T, Ozturk E, Yerci O: MicroRNA expression patterns of tumors in early-onset colorectal cancer patients. J Surg Res 2014, ᅟ:ᅟ-ᅟ. in press
• [31]Nishida N, Yokobori T, Mimori K, Sudo T, Tanaka F, Shibata K, Ishii H, Doki Y, Kuwano H, Mori M: MicroRNA miR-125b is a prognostic marker in human colorectal cancer. Int J Oncol 2011, 38:1437-1443.
• [32]Georgantas RW 3rd, Streicher K, Luo X, Greenlees L, Zhu W, Liu Z, Brohawn P, Morehouse C, Higgs BW, Richman L, Jallal B, Yao Y, Ranade K: MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D. Pigment Cell Melanoma Res 2014, 27:275-286.
• [33]Liu Y, Zhou Y, Feng X, An P, Quan X, Wang H, Ye S, Yu C, He Y, Luo H: MicroRNA-126 functions as a tumor suppressor in colorectal cancer cells by targeting CXCR4 via the AKT and ERK1/2 signaling pathways. Int J Oncol 2014, 44:203-210.
• [34]Poy MN, Eliasson L, Krutzfeldt J, Kuwajima S, Ma X, Macdonald PE, Pfeffer S, Tuschl T, Rajewsky N, Rorsman P, Stoffel M: A pancreatic islet-specific microRNA regulates insulin secretion. Nature 2004, 432:226-230.
• [35]Zhou J, Song S, He S, Zhu X, Zhang Y, Yi B, Zhang B, Qin G, Li D: MicroRNA-375 targets PDK1 in pancreatic carcinoma and suppresses cell growth through the Akt signaling pathway. Int J Mol Med 2014, 33:950-956.
• [36]Faltejskova P, Svoboda M, Srutova K, Mlcochova J, Besse A, Nekvindova J, Radova L, Fabian P, Slaba K, Kiss I, Vyzula R, Slaby O: Identification and functional screening of microRNAs highly deregulated in colorectal cancer. J Cell Mol Med 2012, 16:2655-2666.
• [37]Dai X, Chiang Y, Wang Z, Song Y, Lu C, Gao P, Xu H: Expression levels of microRNA-375 in colorectal carcinoma. Mol Med Rep 2012, 5:1299-1304.
• [38]Wang Y, Tang Q, Li M, Jiang S, Wang X: MicroRNA-375 inhibits colorectal cancer growth by targeting PIK3CA. Biochem Biophys Res Commun 2014, 444:199-204.
• [39]Christensen LL, Holm A, Rantala J, Kallioniemi O, Rasmussen MH, Ostenfeld MS, Dagnaes-Hansen F, Oster B, Schepeler T, Tobiasen H, Thorsen K, Sieber OM, Gibbs P, Lamy P, Hansen TF, Jakobsen A, Riising EM, Helin K, Lubinski J, Hagemann-Madsen R, Laurberg S, Orntoft TF, Andersen CL: Functional screening identifies miRNAs influencing apoptosis and proliferation in colorectal cancer. PLoS One 2014, 9:e96767.
• [40]Papadopoulos GL, Alexiou P, Maragkakis M, Reczko M, Hatzigeorgiou AG: DIANA-mirPath: integrating human and mouse microRNAs in pathways. Bioinformatics 2009, 25:1991-1993.
• [41]Miyachi M, Tsuchiya K, Yoshida H, Yagyu S, Kikuchi K, Misawa A, Iehara T, Hosoi H: Circulating muscle-specific microRNA, miR-206, as a potential diagnostic marker for rhabdomyosarcoma. Biochem Biophys Res Commun 2010, 400:89-93.
• [42]Wu J, Yang T, Li X, Yang Q, Liu R, Huang J, Li Y, Yang C, Jiang Y: Alteration of serum miR-206 and miR-133b is associated with lung carcinogenesis induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Toxicol Appl Pharmacol 2013, 267:238-246.
• [43]Li Y, Hong F, Yu Z: Decreased expression of microRNA-206 in breast cancer and its association with disease characteristics and patient survival. J Int Med Res 2013, 41:596-602.
• [44]Yang Q, Zhang C, Huang B, Li H, Zhang R, Huang Y, Wang J: Downregulation of microRNA-206 is a potent prognostic marker for patients with gastric cancer. Eur J Gastroenterol Hepatol 2013, 25:953-957.
• [45]Alegre E, Sanmamed MF, Rodriguez C, Carranza O, Martin-Algarra S, Gonzalez A: Study of circulating microRNA-125b levels in serum exosomes in advanced melanoma. Arch Pathol Lab Med 2014, 138:828-832.
• [46]Kosaka N, Iguchi H, Yoshioka Y, Takeshita F, Matsuki Y, Ochiya T: Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 2010, 285:17442-17452.
• [47]Brase JC, Johannes M, Schlomm T, Falth M, Haese A, Steuber T, Beissbarth T, Kuner R, Sultmann H: Circulating miRNAs are correlated with tumor progression in prostate cancer. Int J Cancer 2011, 128:608-616.
• [48]Wulfken LM, Moritz R, Ohlmann C, Holdenrieder S, Jung V, Becker F, Herrmann E, Walgenbach-Brunagel G, von Ruecker A, Muller SC, Ellinger J: MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS One 2011, 6:e25787.
• [49]Pigati L, Yaddanapudi SC, Iyengar R, Kim DJ, Hearn SA, Danforth D, Hastings ML, Duelli DM: Selective release of microRNA species from normal and malignant mammary epithelial cells. PLoS One 2010, 5:e13515.
• [50]Zheng H, Fu R, Wang JT, Liu Q, Chen H, Jiang SW: Advances in the techniques for the prediction of microRNA Targets. Int J Mol Sci 2013, 14:8179-8187.
• [51]Xiao F, Zuo Z, Cai G, Kang S, Gao X, Li T: miRecords: an integrated resource for microRNA-target interactions. Nucleic Acids Res 2009, 37:D105-D110.