MicroRNA expression characterizes oligometastasis(es)
Yves A Lussier, H Rosie Xing, Joseph K Salama, Nikolai N Khodarev, Yong Huang, Qingbei Zhang, Sajid A Khan, Xinan Yang, Michael D Hasselle, Thomas E Darga, Renuka Malik, Hanli Fan, Samantha Perakis, Matthew Filippo, Kimberly Corbin, Younghee Lee, Mitchell C Posner, Steven J Chmura, Samuel Hellman, Ralph R Weichselbaum, Yves A Lussier, H Rosie Xing, Joseph K Salama, Nikolai N Khodarev, Yong Huang, Qingbei Zhang, Sajid A Khan, Xinan Yang, Michael D Hasselle, Thomas E Darga, Renuka Malik, Hanli Fan, Samantha Perakis, Matthew Filippo, Kimberly Corbin, Younghee Lee, Mitchell C Posner, Steven J Chmura, Samuel Hellman, Ralph R Weichselbaum
Abstract
Background: Cancer staging and treatment presumes a division into localized or metastatic disease. We proposed an intermediate state defined by ≤ 5 cumulative metastasis(es), termed oligometastases. In contrast to widespread polymetastases, oligometastatic patients may benefit from metastasis-directed local treatments. However, many patients who initially present with oligometastases progress to polymetastases. Predictors of progression could improve patient selection for metastasis-directed therapy.
Methods: Here, we identified patterns of microRNA expression of tumor samples from oligometastatic patients treated with high-dose radiotherapy.
Results: Patients who failed to develop polymetastases are characterized by unique prioritized features of a microRNA classifier that includes the microRNA-200 family. We created an oligometastatic-polymetastatic xenograft model in which the patient-derived microRNAs discriminated between the two metastatic outcomes. MicroRNA-200c enhancement in an oligometastatic cell line resulted in polymetastatic progression.
Conclusions: These results demonstrate a biological basis for oligometastases and a potential for using microRNA expression to identify patients most likely to remain oligometastatic after metastasis-directed treatment.
Conflict of interest statement
Competing Interests: The authors have declared that no competing interests exist.
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References
- Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol 2011
- Staren ED, Salerno C, Rongione A, Witt TR, Faber LP. Pulmonary resection for metastatic breast cancer. Arch Surg. 1992;127:1282–1284.
- Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13:8–10.
- Fong Y, Cohen AM, Fortner JG, Enker WE, Turnbull AD, et al. Liver resection for colorectal metastases. J Clin Oncol. 1997;15:938–946.
- Tomlinson JS, Jarnagin WR, DeMatteo RP, Fong Y, Kornprat P, et al. Actual 10-year survival after resection of colorectal liver metastases defines cure. J Clin Oncol. 2007;25:4575–4580.
- Tanvetyanon T, Robinson LA, Schell MJ, Strong VE, Kapoor R, et al. Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis. J Clin Oncol. 2008;26:1142–1147.
- Mehta N, Mauer AM, Hellman S, Haraf DJ, Cohen EE, et al. Analysis of further disease progression in metastatic non-small cell lung cancer: implications for locoregional treatment. Int J Oncol. 2004;25:1677–1683.
- Milano MT, Katz AW, Muhs AG, Philip A, Buchholz DJ, et al. A prospective pilot study of curative-intent stereotactic body radiation therapy in patients with 5 or fewer oligometastatic lesions. Cancer. 2008;112:650–658.
- Salama JK, Chmura SJ, Mehta N, Yenice KM, Stadler WM, et al. An initial report of a radiation dose-escalation trial in patients with one to five sites of metastatic disease. Clin Cancer Res. 2008;14:5255–5259.
- Rusthoven KE, Kavanagh BD, Burri SH, Chen C, Cardenes H, et al. Multi-institutional phase I/II trial of stereotactic body radiation therapy for lung metastases. J Clin Oncol. 2009;27:1579–1584.
- Hoyer M, Roed H, Traberg Hansen A, Ohlhuis L, Petersen J, et al. Phase II study on stereotactic body radiotherapy of colorectal metastases. Acta Oncol. 2006;45:823–830.
- Milano MT, Constine LS, Okunieff P. Normal tissue toxicity after small field hypofractionated stereotactic body radiation. Radiat Oncol. 2008;3:36.
- Schefter TE, Kavanagh BD, Timmerman RD, Cardenes HR, Baron A, et al. A phase I trial of stereotactic body radiation therapy (SBRT) for liver metastases. Int J Radiat Oncol Biol Phys. 2005;62:1371–1378.
- Aoyama H, Shirato H, Tago M, Nakagawa K, Toyoda T, et al. Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial. JAMA. 2006;295:2483–2491.
- Dvinge H, Bertone P. HTqPCR: high-throughput analysis and visualization of quantitative real-time PCR data in R. Bioinformatics. 2009;25:3325–3326.
- Parmigiani G, Garrett E, Irizarry R, Zeger S, Li C, et al. DNA-Chip Analyzer (dChip). In: Gail M, Krickeberg K, Samet J, Tsiatis A, Wong W, editors. The Analysis of Gene Expression Data. Springer London; 2003. pp. 120–141.
- JEAN THIOULOUSE DC, SYLVAIN DOLEÂ DEC, OLIVIER J-M. ADE-4: a multivariate analysis and graphical display software. Statistics and Computing. 1997;7:75–83.
- Hand DJTR. A Simple Generalisation of the Area Under the ROC Curve for Multiple Class Classification Problems. Machine Learning. 2001;45
- Ihaka R, Gentleman R. A Language for Data Analysis and Graphics. J Comput Graph Stat. 1996;5:299–314.
- Li X, Wang J, An Z, Yang M, Baranov E, et al. Optically imageable metastatic model of human breast cancer. Clin Exp Metastasis. 2002;19:347–350.
- Zhang Q, Bindokas V, Shen J, Fan H, Hoffman RM, et al. Time-course imaging of therapeutic functional tumor vascualr normalization by anti-angiogenic agents. Mol Cancer Ther. 2011;10:1173–1184.
- Lee Y, Yang X, Huang Y, Fan H, Zhang Q, et al. Network modeling identifies molecular functions targeted by miR-204 to suppress head and neck tumor metastasis. PLoS Comput Biol. 2010;6:e1000730.
- Giavazzi R, Garofalo A. Syngeneic murine metastasis models : b16 melanoma. Methods Mol Med. 2001;58:223–229.
- Yachida S, Jones S, Bozic I, Antal T, Leary R, et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature. 2010;467:1114–1117.
- Bendoraite A, Knouf EC, Garg KS, Parkin RK, Kroh EM, et al. Regulation of miR-200 family microRNAs and ZEB transcription factors in ovarian cancer: evidence supporting a mesothelial-to-epithelial transition. Gynecol Oncol. 2010;116:117–125.
- Korpal M, Kang Y. The emerging role of miR-200 family of microRNAs in epithelial-mesenchymal transition and cancer metastasis. RNA Biol. 2008;5:115–119.
- Dykxhoorn DM, Wu Y, Xie H, Yu F, Lal A, et al. miR-200 enhances mouse breast cancer cell colonization to form distant metastases. PLoS One. 2009;4:e7181.
- Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008;283:14910–14914.
- Bonnomet A, Brysse A, Tachsidis A, Waltham M, Thompson EW, et al. Epithelial-to-mesenchymal transitions and circulating tumor cells. J Mammary Gland Biol Neoplasia. 2010;15:261–273.
- Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, et al. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 2008;68:7846–7854.
- Tryndyak VP, Beland FA, Pogribny IP. E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer. 2010;126:2575–2583.
- Gao S, Alarcon C, Sapkota G, Rahman S, Chen PY, et al. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell. 2009;36:457–468.
- Zheng Y, Fischer DJ, Santos MF, Tigyi G, Pasteris NG, et al. The faciogenital dysplasia gene product FGD1 functions as a Cdc42Hs-specific guanine-nucleotide exchange factor. J Biol Chem. 1996;271:33169–33172.
- Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451:147–152.
- Roth C, Rack B, Muller V, Janni W, Pantel K, et al. Circulating microRNAs as blood-based markers for patients with primary and metastatic breast cancer. Breast Cancer Res. 2010;12:R90.
- Ory B, Ellisen LW. A microRNA-dependent circuit controlling p63/p73 homeostasis: p53 family cross-talk meets therapeutic opportunity. Oncotarget. 2:259–264.
- Nohata N, Sone Y, Hanazawa T, Fuse M, Kikkawa N, et al. miR-1 as a tumor suppressive microRNA targeting TAGLN2 in head and neck squamous cell carcinoma. Oncotarget. 2011;2:29–42.
- Valastyan S, Weinberg RA. MicroRNAs: Crucial multi-tasking components in the complex circuitry of tumor metastasis. Cell Cycle. 2009;8:3506–3512.
- Valastyan S, Weinberg RA. miR-31: a crucial overseer of tumor metastasis and other emerging roles. Cell Cycle. 2010;9:2124–2129.
- Smits M, Nilsson J, Mir SE, van der Stoop PM, Hulleman E, et al. miR-101 is down-regulated in glioblastoma resulting in EZH2-induced proliferation, migration, and angiogenesis. Oncotarget. 2010;1:710–720.
- Schmidt-Kittler O, Zhu J, Yang J, Liu G, Hendricks W, et al. PI3Kalpha inhibitors that inhibit metastasis. Oncotarget. 2011;1:339–348.
- Noonan EJ, Place RF, Basak S, Pookot D, Li LC. miR-449a causes Rb-dependent cell cycle arrest and senescence in prostate cancer cells. Oncotarget. 2010;1:349–358.
- Torres L, Ribeiro FR, Pandis N, Andersen JA, Heim S, et al. Intratumor genomic heterogeneity in breast cancer with clonal divergence between primary carcinomas and lymph node metastases. Breast Cancer Res Treat. 2007;102:143–155.
- Liu W, Laitinen S, Khan S, Vihinen M, Kowalski J, et al. Copy number analysis indicates monoclonal origin of lethal metastatic prostate cancer. Nat Med. 2009;15:559–565.
- Campbell PJ, Yachida S, Mudie LJ, Stephens PJ, Pleasance ED, et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 2010;467:1109–1113.
- Klein CA, Blankenstein TJ, Schmidt-Kittler O, Petronio M, Polzer B, et al. Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet. 2002;360:683–689.
- Vrba L, Jensen TJ, Garbe JC, Heimark RL, Cress AE, et al. Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One. 2010;5:e8697.
- Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10:593–601.
- Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, et al. Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med 2011
- Elson-Schwab I, Lorentzen A, Marshall CJ. MicroRNA-200 family members differentially regulate morphological plasticity and mode of melanoma cell invasion. PLoS One. 2010;5
- Soond SM, Chantry A. Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFbeta signalling and EMT. Oncogene 2011
- Bandyopadhyay A, Agyin JK, Wang L, Tang Y, Lei X, et al. Inhibition of pulmonary and skeletal metastasis by a transforming growth factor-beta type I receptor kinase inhibitor. Cancer Res. 2006;66:6714–6721.
- Buck MB, Fritz P, Dippon J, Zugmaier G, Knabbe C. Prognostic significance of transforming growth factor beta receptor II in estrogen receptor-negative breast cancer patients. Clin Cancer Res. 2004;10:491–498.
- Siegel PM, Shu W, Cardiff RD, Muller WJ, Massague J. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci U S A. 2003;100:8430–8435.
- Gregory PA, Bracken CP, Smith E, Bert AG, Wright JA, et al. An autocrine TGF-{beta}/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition. Mol Biol Cell 2011
- Li R, Liang J, Ni S, Zhou T, Qing X, et al. A mesenchymal-to-epithelial transition initiates and is required for the nuclear reprogramming of mouse fibroblasts. Cell Stem Cell. 2010;7:51–63.
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