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BMC Cancer
Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Stage and tissue-specific prognostic impact of miR-182 in NSCLC

Authors: Helge Stenvold, Tom Donnem, Sigve Andersen, Samer Al-Saad, Lill-Tove Busund, Roy M Bremnes

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

MicroRNA (miR)-182 is frequently upregulated in cancers, has generally been viewed as an oncogene and is possibly connected to angiogenesis. We aimed to explore what impact miR-182 has in non-small cell lung cancer (NSCLC), and more explicitly its correlation with angiogenic markers.

Methods

From 335 unselected stage I to IIIA NSCLC carcinomas, duplicate tumor and tumor-associated stromal cores were collected in tissue microarray blocks (TMAs). In situ hybridization (ISH) was used to detect the expression of miR-182 in tumor cells, and immunohistochemistry (IHC) was used to detect the expression of angiogenesis related protein markers.

Results

In univariate analyses, high tumor cell expression of miR-182 was a positive prognostic factor for patients with squamous cell carcinoma (SCC, P = 0.042) and stage II patients (P = 0.003). Also in the multivariate analysis, high tumor cell miR-182 expression was associated with a good prognosis in the same groups (SCC: HR 0.57, CI 95% 0.33-0.99, P = 0.048; stage II: HR 0.50, CI 95% 0.28-0.90, P = 0.020). We found significant correlations between miR-182 and the angiogenesis related markers FGF2, HIF2α and MMP-7.

Conclusion

In patients with SCC and in stage II patients, high tumor cell miR-182 expression is an independent positive prognostic factor.
Appendix
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Literature
1.
Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.CrossRefPubMed
2.
Drilon A, Rekhtman N, Ladanyi M, Paik P: Squamous-cell carcinomas of the lung: emerging biology, controversies, and the promise of targeted therapy. Lancet Oncol. 2012, 13: e418-e426. 10.1016/S1470-2045(12)70291-7.CrossRefPubMed
3.
Ma PC: Personalized targeted therapy in advanced non-small cell lung cancer. Cleve Clin J Med. 2012, 79 (Electronic Suppl 1): eS56-eS60.PubMed
4.
Kasinski AL, Slack FJ: Epigenetics and genetics. MicroRNAs en route to the clinic: progress in validating and targeting microRNAs for cancer therapy. Nat Rev Cancer. 2011, 11: 849-864. 10.1038/nrc3166.CrossRefPubMedPubMedCentral
5.
Calin GA, Sevignani C, Dumitru CD, Hyslop T, Noch E, Yendamuri S, Shimizu M, Rattan S, Bullrich F, Negrini M, Croce CM: Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. Proc Natl Acad Sci U S A. 2004, 101: 2999-3004. 10.1073/pnas.0307323101.CrossRefPubMedPubMedCentral
6.
Calin GA, Croce CM: MicroRNA signatures in human cancers. Nat Rev Cancer. 2006, 6: 857-866. 10.1038/nrc1997.CrossRefPubMed
7.
Cho WC, Chow AS, Au JS: Restoration of tumour suppressor hsa-miR-145 inhibits cancer cell growth in lung adenocarcinoma patients with epidermal growth factor receptor mutation. Eur J Cancer. 2009, 45: 2197-2206. 10.1016/j.ejca.2009.04.039.CrossRefPubMed
8.
Guan P, Yin Z, Li X, Wu W, Zhou B: Meta-analysis of human lung cancer microRNA expression profiling studies comparing cancer tissues with normal tissues. J Exp Clin Cancer Res. 2012, 31: 54-10.1186/1756-9966-31-54.CrossRefPubMedPubMedCentral
9.
Tan X, Qin W, Zhang L, Hang J, Li B, Zhang C, Wan J, Zhou F, Shao K, Sun Y, Wu J, Zhang X, Qiu B, Li N, Shi S, Feng X, Zhao S, Wang Z, Zhao X, Chen Z, Mitchelson K, Cheng J, Guo Y, He J: A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis. Clin Cancer Res. 2011, 17: 6802-6811. 10.1158/1078-0432.CCR-11-0419.CrossRefPubMed
10.
Zheng D, Haddadin S, Wang Y, Gu LQ, Perry MC, Freter CE, Wang MX: Plasma microRNAs as novel biomarkers for early detection of lung cancer. Int J Clin Exp Pathol. 2011, 4: 575-586.PubMedPubMedCentral
11.
Zhu W, Liu X, He J, Chen D, Hunag Y, Zhang YK: Overexpression of members of the microRNA-183 family is a risk factor for lung cancer: a case control study. BMC Cancer. 2011, 11: 393-10.1186/1471-2407-11-393.CrossRefPubMedPubMedCentral
12.
Jiang L, Mao P, Song L, Wu J, Huang J, Lin C, Yuan J, Qu L, Cheng SY, Li J: miR-182 as a prognostic marker for glioma progression and patient survival. Am J Pathol. 2010, 177: 29-38. 10.2353/ajpath.2010.090812.CrossRefPubMedPubMedCentral
13.
Segura MF, Hanniford D, Menendez S, Reavie L, Zou X, Alvarez-Diaz S, Zakrzewski J, Blochin E, Rose A, Bogunovic D, Polsky D, Wei J, Lee P, Belitskaya-Levy I, Bhardwaj N, Osman I, Hernando E: Aberrant miR-182 expression promotes melanoma metastasis by repressing FOXO3 and microphthalmia-associated transcription factor. Proc Natl Acad Sci U S A. 2009, 106: 1814-1819. 10.1073/pnas.0808263106.CrossRefPubMedPubMedCentral
14.
Poell JB, van Haastert RJ, de Gunst T, Schultz IJ, Gommans WM, Verheul M, Cerisoli F, van Noort PI, Prevost GP, Schaapveld RQ, Cuppen E: A functional screen identifies specific microRNAs capable of inhibiting human melanoma cell viability. PLoS One. 2012, 7: e43569-10.1371/journal.pone.0043569.CrossRefPubMedPubMedCentral
15.
Sun Y, Fang R, Li C, Li L, Li F, Ye X, Chen H: Hsa-mir-182 suppresses lung tumorigenesis through down regulation of RGS17 expression in vitro. Biochem Biophys Res Commun. 2010, 396: 501-507. 10.1016/j.bbrc.2010.04.127.CrossRefPubMed
16.
Yan D, Dong XD, Chen X, Yao S, Wang L, Wang J, Wang C, Hu DN, Qu J, Tu L: Role of microRNA-182 in posterior uveal melanoma: regulation of tumor development through MITF, BCL2 and cyclin D2. PLoS One. 2012, 7: e40967-10.1371/journal.pone.0040967.CrossRefPubMedPubMedCentral
17.
Donnem T, Fenton CG, Lonvik K, Berg T, Eklo K, Andersen S, Stenvold H, Al-Shibli K, Al-Saad S, Bremnes RM, Busund LT: MicroRNA signatures in tumor tissue related to angiogenesis in Non-small cell lung cancer. PLoS One. 2012, 7: e29671-10.1371/journal.pone.0029671.CrossRefPubMedPubMedCentral
18.
Rami-Porta R, Chansky K, Goldstraw P: Updated lung cancer staging system. Future Oncol. 2009, 5: 1545-1553. 10.2217/fon.09.131.CrossRefPubMed
19.
Donnem T, Al-Saad S, Al-Shibli K, Delghandi MP, Persson M, Nilsen MN, Busund LT, Bremnes RM: Inverse prognostic impact of angiogenic marker expression in tumor cells versus stromal cells in non small cell lung cancer. Clin Cancer Res. 2007, 13: 6649-6657. 10.1158/1078-0432.CCR-07-0414.CrossRefPubMed
20.
Jorgensen S, Baker A, Moller S, Nielsen BS: Robust one-day in situ hybridization protocol for detection of microRNAs in paraffin samples using LNA probes. Methods. 2010, 52: 375-381. 10.1016/j.ymeth.2010.07.002.CrossRefPubMed
21.
Andersen S, Eilertsen M, Donnem T, Al-Shibli K, Al-Saad S, Busund LT, Bremnes RM: Diverging prognostic impacts of hypoxic markers according to NSCLC histology. Lung Cancer. 2011, 72: 294-302. 10.1016/j.lungcan.2010.10.006.CrossRefPubMed
22.
Donnem T, Al-Shibli K, Al-Saad S, Busund LT, Bremnes RM: Prognostic impact of fibroblast growth factor 2 in non-small cell lung cancer: coexpression with VEGFR-3 and PDGF-B predicts poor survival. J Thorac Oncol. 2009, 4: 578-585. 10.1097/JTO.0b013e31819f2e38.CrossRefPubMed
23.
Stenvold H, Donnem T, Andersen S, Al-Saad S, Al-Shibli K, Busund LT, Bremnes RM: Overexpression of matrix metalloproteinase-7 and −9 in NSCLC tumor and stromal cells: correlation with a favorable clinical outcome. Lung Cancer. 2012, 75: 235-241. 10.1016/j.lungcan.2011.06.010.CrossRefPubMed
24.
Barshack I, Lithwick-Yanai G, Afek A, Rosenblatt K, Tabibian-Keissar H, Zepeniuk M, Cohen L, Dan H, Zion O, Strenov Y, Polak-Charcon S, Perelman M: MicroRNA expression differentiates between primary lung tumors and metastases to the lung. Pathol Res Pract. 2010, 206: 578-584. 10.1016/j.prp.2010.03.005.CrossRefPubMed
25.
Barshack I, Meiri E, Rosenwald S, Lebanony D, Bronfeld M, Aviel-Ronen S, Rosenblatt K, Polak-Charcon S, Leizerman I, Ezagouri M, Zepeniuk M, Shabes N, Cohen L, Tabak S, Cohen D, Bentwich Z, Rosenfeld N: Differential diagnosis of hepatocellular carcinoma from metastatic tumors in the liver using microRNA expression. Int J Biochem Cell Biol. 2010, 42: 1355-1362. 10.1016/j.biocel.2009.02.021.CrossRefPubMed
26.
27.
Donnem T, Eklo K, Berg T, Sorbye SW, Lonvik K, Al-Saad S, Al-Shibli K, Andersen S, Stenvold H, Bremnes RM, Busund LT: Prognostic impact of MiR-155 in non-small cell lung cancer evaluated by in situ hybridization. J Transl Med. 2011, 9: 6-10.1186/1479-5876-9-6.CrossRefPubMedPubMedCentral
28.
Huynh C, Segura MF, Gaziel-Sovran A, Menendez S, Darvishian F, Chiriboga L, Levin B, Meruelo D, Osman I, Zavadil J, Marcusson EG, Hernando E: Efficient in vivo microRNA targeting of liver metastasis. Oncogene. 2011, 30: 1481-1488. 10.1038/onc.2010.523.CrossRefPubMed
29.
Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, Beech J, Kulshrestha R, Abdelmohsen K, Weinstock DM, Gorospe M, Harris AL, Helleday T, Chowdhury D: miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors. Mol Cell. 2011, 41: 210-220. 10.1016/j.molcel.2010.12.005.CrossRefPubMed
30.
Tang T, Wong HK, Gu W, Yu MY, To KF, Wang CC, Wong YF, Cheung TH, Chung TK, Choy KW: MicroRNA-182 plays an onco-miRNA role in cervical cancer. Gynecol Oncol. 2013, 129: 199-208. 10.1016/j.ygyno.2012.12.043.CrossRefPubMed
31.
Kong WQ, Bai R, Liu T, Cai CL, Liu M, Li X, Tang H: MicroRNA-182 targets cAMP-responsive element-binding protein 1 and suppresses cell growth in human gastric adenocarcinoma. FEBS J. 2012, 279: 1252-1260. 10.1111/j.1742-4658.2012.08519.x.CrossRefPubMed
32.
Zhang L, Liu T, Huang Y, Liu J: microRNA-182 inhibits the proliferation and invasion of human lung adenocarcinoma cells through its effect on human cortical actin-associated protein. Int J Mol Med. 2011, 28: 381-388.PubMed
33.
Zhou W, Feng X, Wu Y, Benge J, Zhang Z, Chen Z: FGF-receptor substrate 2 functions as a molecular sensor integrating external regulatory signals into the FGF pathway. Cell Res. 2009, 19: 1165-1177. 10.1038/cr.2009.95.CrossRefPubMed
34.
Ding K, Lopez-Burks M, Sanchez-Duran JA, Korc M, Lander AD: Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J Cell Biol. 2005, 171: 729-738. 10.1083/jcb.200508010.CrossRefPubMedPubMedCentral
35.
Holnthoner W, Kerenyi M, Groger M, Kratochvill F, Petzelbauer P: Regulation of matrilysin expression in endothelium by fibroblast growth factor-2. Biochem Biophys Res Commun. 2006, 342: 725-733. 10.1016/j.bbrc.2006.02.011.CrossRefPubMed
Metadata
Title
Stage and tissue-specific prognostic impact of miR-182 in NSCLC
Authors
Helge Stenvold
Tom Donnem
Sigve Andersen
Samer Al-Saad
Lill-Tove Busund
Roy M Bremnes
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-138

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