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01-04-2016 | Original Article

miRNA profiling in serum and tissue samples to assess noninvasive biomarkers for NSCLC clinical outcome

Authors: D. Petriella, S. De Summa, R. Lacalamita, D. Galetta, A. Catino, A. F. Logroscino, O. Palumbo, M. Carella, F. A. Zito, G. Simone, S. Tommasi

Published in: Tumor Biology | Issue 4/2016

Abstract

In NSCLC, the altered expression of some miRNAs in primary tumor tissues has been correlated with diagnosis and prognosis, while the role of circulating miRNAs as cancer biomarkers is currently emerging. MiRNA expression profile through miRNA Affymetrix array was evaluated on a training set formed by the tumor component (n = 30 NSCLC serum, n = 11/30 tumor tissues) and the control component (n = 10 healthy serum and n = 11/30 noncancerous counterparts). Statistical analyses highlighted the following: a = 55 miRNAs deregulated in tumor serum, b = 27 miRNAs deregulated in tumor tissues, and c = 2 miRNAs deregulated both in tumor serum and in tumor tissues. MiRwalk tool and enrichment pathway analyses selected some miRNAs whose target genes are correlated with the main pathways involved in NSCLC tumorigenesis. The altered expression of the selected miR-486-5p (a), miR-29c* (b), and miR-133a (c) was confirmed in the validation set (n = 40). MiR-486-5p had a higher expression in tumor serum than in tumor tissues (P = 0.004), and miR-29c* showed a lower expression in tumor tissues than in tumor serum (P < 0.001). MiR-133a had a not different expression in both tumor serum and tumor tissues (P = 0.07). The low level of miR-486-5p expression in the serum of affected patients was associated with a worse time to progression of disease (P = 0.010), and serum level of miR-486-5p was a significant prognostic indicator of NSCLC (adjusted hazard ratio = 0.179, P = 0.019). These data suggest the possibility to monitor affected patients through serum and/or tissue samples, analyzing the altered expression of specific miRNAs, in order to detect prognostic biomarkers in the NSCLC.

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Zochbauer-Muller S, Fong KM, Maitra A, Lam S, Geradts J, Ashfaq R, et al. 5′ CpG island methylation of the FHIT gene is correlated with loss of gene expression in lung and breast cancer. Cancer Res. 2001;61(9):3581–5.PubMed

Mao L, Hruban RH, Boyle JO, Tockman M, Sidransky D. Detection of oncogene mutations in sputum precedes diagnosis of lung cancer. Cancer Res. 1994;54(7):1634–7.PubMed

Sakashita S, Sakashita M, Sound Tsao M. Genes and pathology of non-small cell lung carcinoma. Semin Oncol. 2014;41(1):28–39. doi:10.1053/j.seminoncol.2013.12.008.CrossRefPubMed

Hirsch FR, Franklin WA, Gazdar AF, Bunn Jr PA. Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. Clini Cancer Res: Off J Am Cancer Res. 2001;7(1):5–22.

Yanaihara N, Caplen N, Bowman E, Seike M, Kumamoto K, Yi M, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9(3):189–98. doi:10.1016/j.ccr.2006.01.025.CrossRefPubMed

Croce CM. Causes and consequences of microRNA dysregulation in cancer. Nat Rev Genet. 2009;10(10):704–14. doi:10.1038/nrg2634.CrossRefPubMedPubMedCentral

Chen L, Jin H. MicroRNAs as novel biomarkers in the diagnosis of non-small cell lung cancer: a meta-analysis based on 20 studies. Tumour Biol : J Int Soc Oncodev Biol Med. 2014;35(9):9119–29. doi:10.1007/s13277-014-2188-2.CrossRef

Lin PY, Yu SL, Yang PC. MicroRNA in lung cancer. Br J Cancer. 2010;103(8):1144–8. doi:10.1038/sj.bjc.6605901.CrossRefPubMedPubMedCentral

Wang Q, Wang S, Wang H, Li P, Ma Z. MicroRNAs: novel biomarkers for lung cancer diagnosis, prediction and treatment. Exp Biol Med. 2012;237(3):227–35. doi:10.1258/ebm.2011.011192.CrossRef

10.

Vannini I, Fanini F, Fabbri M. MicroRNAs as lung cancer biomarkers and key players in lung carcinogenesis. Clin Biochem. 2013;46(10–11):918–25. doi:10.1016/j.clinbiochem.2013.01.024.CrossRefPubMed

11.

Weber DG, Casjens S, Rozynek P, Lehnert M, Zilch-Schoneweis S, Bryk O, et al. Assessment of mRNA and microRNA stabilization in peripheral human blood for multicenter studies and biobanks. Biomark Insights. 2010;5:95–102.CrossRefPubMedPubMedCentral

12.

Redova M, Sana J, Slaby O. Circulating miRNAs as new blood-based biomarkers for solid cancers. Future Oncol. 2013;9(3):387–402. doi:10.2217/fon.12.192.CrossRefPubMed

13.

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 : CR. 2012;31:54. doi:10.1186/1756-9966-31-54.CrossRefPubMedPubMedCentral

14.

Chen X, Hu Z, Wang W, Ba Y, Ma L, Zhang C, et al. Identification of ten serum microRNAs from a genome-wide serum microRNA expression profile as novel noninvasive biomarkers for nonsmall cell lung cancer diagnosis. Int J Cancer J int du cancer. 2012;130(7):1620–8. doi:10.1002/ijc.26177.CrossRef

15.

Bianchi F, Nicassio F, Marzi M, Belloni E, Dall’olio V, Bernard L, et al. A serum circulating miRNA diagnostic test to identify asymptomatic high-risk individuals with early stage lung cancer. EMBO Mol Med. 2011;3(8):495–503. doi:10.1002/emmm.201100154.CrossRefPubMedPubMedCentral

16.

Boeri M, Pastorino U, Sozzi G. Role of microRNAs in lung cancer: microRNA signatures in cancer prognosis. Cancer J. 2012;18(3):268–74. doi:10.1097/PPO.0b013e318258b743.CrossRefPubMed

17.

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.CrossRefPubMedPubMedCentral

18.

Rabinowits G, Gercel-Taylor C, Day JM, Taylor DD, Kloecker GH. Exosomal microRNA: a diagnostic marker for lung cancer. Clin Lung Cancer. 2009;10(1):42–6. doi:10.3816/CLC.2009.n.006.CrossRefPubMed

19.

Gallo A, Tandon M, Alevizos I, Illei GG. The majority of microRNAs detectable in serum and saliva is concentrated in exosomes. PLoS One. 2012;7(3), e30679. doi:10.1371/journal.pone.0030679.CrossRefPubMedPubMedCentral

20.

Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res. 2008;18(10):997–1006. doi:10.1038/cr.2008.282.CrossRefPubMed

21.

Tavis WD, Brambilla E, Müller-Hermalink HK. Pathology and genetics of tumors of lung, pleura, thymus and heart. Lion: IARC-Press; 2004.

22.

Mirsadraee S, Oswal D, Alizadeh Y, Caulo A, Van Beek Jr E. The 7th lung cancer TNM classification and staging system: review of the changes and implications. World J Radiol. 2012;4(4):128–34. doi:10.4329/wjr.v4.i4.128.CrossRefPubMedPubMedCentral

23.

Kirschner MB, Kao SC, Edelman JJ, Armstrong NJ, Vallely MP, van Zandwijk N, et al. Haemolysis during sample preparation alters microRNA content of plasma. PLoS One. 2011;6(9), e24145. doi:10.1371/journal.pone.0024145.CrossRefPubMedPubMedCentral

24.

Kennedy JB, Maehara KT, Baker AM. Cell and platelet stability in disodium and tripotassium edta. Am J Med Technol. 1981;47(2):89–93.PubMed

25.

Kroh EM, Parkin RK, Mitchell PS, Tewari M. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods. 2010;50(4):298–301. doi:10.1016/j.ymeth.2010.01.032.CrossRefPubMedPubMedCentral

26.

Dweep H, Sticht C, Pandey P, Gretz N. miRWalk--database: prediction of possible miRNA binding sites by “walking” the genes of three genomes. J Biomed Inform. 2011;44(5):839–47. doi:10.1016/j.jbi.2011.05.002.CrossRefPubMed

27.

da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57. doi:10.1038/nprot.2008.211.CrossRef

28.

Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, et al. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733–41. doi:10.1373/clinchem.2010.147405.CrossRefPubMedPubMedCentral

29.

Petriella D, Galetta D, Rubini V, Savino E, Paradiso A, Simone G, et al. Molecular profiling of thin-prep FNA samples in assisting clinical management of non-small-cell lung cancer. Mol Biotechnol. 2013;54(3):913–9. doi:10.1007/s12033-012-9640-6.CrossRefPubMed

30.

Fortunato O, Boeri M, Verri C, Conte D, Mensah M, Suatoni P, et al. Assessment of circulating microRNAs in plasma of lung cancer patients. Molecules. 2014;19(3):3038–54. doi:10.3390/molecules19033038.CrossRefPubMed

31.

Chen Q, Si Q, Xiao S, Xie Q, Lin J, Wang C, et al. Prognostic significance of serum miR-17-5p in lung cancer. Med Oncol. 2013;30(1):353. doi:10.1007/s12032-012-0353-2.CrossRefPubMed

32.

Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103(7):2257–61. doi:10.1073/pnas.0510565103.CrossRefPubMedPubMedCentral

33.

Markou A, Sourvinou I, Vorkas PA, Yousef GM, Lianidou E. Clinical evaluation of microRNA expression profiling in non small cell lung cancer. Lung Cancer. 2013;81(3):388–96. doi:10.1016/j.lungcan.2013.05.007.CrossRefPubMed

34.

Boeri M, Verri C, Conte D, Roz L, Modena P, Facchinetti F, et al. MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer. Proc Natl Acad Sci U S A. 2011;108(9):3713–8. doi:10.1073/pnas.1100048108.CrossRefPubMedPubMedCentral

35.

Yu SL, Chen HY, Chang GC, Chen CY, Chen HW, Singh S, et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell. 2008;13(1):48–57. doi:10.1016/j.ccr.2007.12.008.CrossRefPubMed

36.

Yu L, Todd NW, Xing L, Xie Y, Zhang H, Liu Z, et al. Early detection of lung adenocarcinoma in sputum by a panel of microRNA markers. Int J Cancer J int du cancer. 2010;127(12):2870–8. doi:10.1002/ijc.25289.CrossRef

37.

Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol : Off J Am Soc Clin Oncol. 2010;28(10):1721–6. doi:10.1200/JCO.2009.24.9342.CrossRef

38.

Tan X, Qin W, Zhang L, Hang J, Li B, Zhang C, et al. A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31 for prognosis. Clin Cancer Res : Off J Am Assoc Cancer Res. 2011;17(21):6802–11. doi:10.1158/1078-0432.CCR-11-0419.CrossRef

39.

Small EM, O’Rourke JR, Moresi V, Sutherland LB, McAnally J, Gerard RD, et al. Regulation of PI3-kinase/Akt signaling by muscle-enriched microRNA-486. Proc Natl Acad Sci U S A. 2010;107(9):4218–23. doi:10.1073/pnas.1000300107.CrossRefPubMedPubMedCentral

40.

Huang XP, Hou J, Shen XY, Huang CY, Zhang XH, Xie YA, et al. MicroRNA-486-5p, which is downregulated in hepatocellular carcinoma, suppresses tumor growth by targeting PIK3R1. FEBS J. 2015;282(3):579–94. doi:10.1111/febs.13167.CrossRefPubMed

41.

Peng Y, Dai Y, Hitchcock C, Yang X, Kassis ES, Liu L, et al. Insulin growth factor signaling is regulated by microRNA-486, an underexpressed microRNA in lung cancer. Proc Natl Acad Sci U S A. 2013;110(37):15043–8. doi:10.1073/pnas.1307107110.CrossRefPubMedPubMedCentral

42.

Wang J, Tian X, Han R, Zhang X, Wang X, Shen H, et al. Downregulation of miR-486-5p contributes to tumor progression and metastasis by targeting protumorigenic ARHGAP5 in lung cancer. Oncogene. 2014;33(9):1181–9. doi:10.1038/onc.2013.42.CrossRefPubMed

43.

Shen J, Liu Z, Todd NW, Zhang H, Liao J, Yu L, et al. Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers. BMC Cancer. 2011;11:374. doi:10.1186/1471-2407-11-374.CrossRefPubMedPubMedCentral

44.

Pang W, Tian X, Bai F, Han R, Wang J, Shen H, et al. Pim-1 kinase is a target of miR-486-5p and eukaryotic translation initiation factor 4E, and plays a critical role in lung cancer. Mol Cancer. 2014;13:240. doi:10.1186/1476-4598-13-240.CrossRefPubMedPubMedCentral

45.

Pass HI, Goparaju C, Ivanov S, Donington J, Carbone M, Hoshen M, et al. hsa-miR-29c* is linked to the prognosis of malignant pleural mesothelioma. Cancer Res. 2010;70(5):1916–24. doi:10.1158/0008-5472.CAN-09-3993.CrossRefPubMedPubMedCentral

46.

Zhu W, He J, Chen D, Zhang B, Xu L, Ma H, et al. Expression of miR-29c, miR-93, and miR-429 as potential biomarkers for detection of early stage non-small lung cancer. PLoS One. 2014;9(2), e87780. doi:10.1371/journal.pone.0087780.CrossRefPubMedPubMedCentral

47.

Du L, Borkowski R, Zhao Z, Ma X, Yu X, Xie XJ, et al. A high-throughput screen identifies miRNA inhibitors regulating lung cancer cell survival and response to paclitaxel. RNA Biol. 2013;10(11):1700–13. doi:10.4161/rna.26541.CrossRefPubMedPubMedCentral

48.

Moriya Y, Nohata N, Kinoshita T, Mutallip M, Okamoto T, Yoshida S, et al. Tumor suppressive microRNA-133a regulates novel molecular networks in lung squamous cell carcinoma. J Hum Genet. 2012;57(1):38–45. doi:10.1038/jhg.2011.126.CrossRefPubMed

Title: miRNA profiling in serum and tissue samples to assess noninvasive biomarkers for NSCLC clinical outcome
Authors: D. Petriella
S. De Summa
R. Lacalamita
D. Galetta
A. Catino
A. F. Logroscino
O. Palumbo
M. Carella
F. A. Zito
G. Simone
S. Tommasi
Publication date: 01-04-2016
Publisher: Springer Netherlands
Published in: Tumor Biology / Issue 4/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI: https://doi.org/10.1007/s13277-015-4391-1

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