CoChat
Sign Up
Cited by 605

MicroRNA signatures in tissues and plasma predict development and prognosis of computed tomography detected lung cancer

Boeri, Mattia, Verri, Carla, Conte, Davide, Roz, Luca, Modena, Piergiorgio, Facchinetti, Federica, Calabrò, Elisa, Croce, Carlo M. +2 more·2011·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.1100048108
Open this paper in CoChat — free account

Abstract

The efficacy of computed tomography (CT) screening for early lung cancer detection in heavy smokers is currently being tested by a number of randomized trials. Critical issues remain the frequency of unnecessary treatments and impact on mortality, indicating the need for biomarkers of aggressive disease. We explored microRNA (miRNA) expression profiles of lung tumors, normal lung tissues and plasma samples from cases with variable prognosis identified in a completed spiral-CT screening trial with extensive follow-up. miRNA expression patterns significantly distinguished: ( i ) tumors from normal lung tissues, ( ii ) tumor histology and growth rate, ( iii ) clinical outcome, and ( iv ) year of lung cancer CT detection. Interestingly, miRNA profiles in normal lung tissues also displayed remarkable associations with clinical features, suggesting the influence of a permissive microenvironment for tumor development. miRNA expression analyses in plasma samples collected 1–2 y before the onset of disease, at the time of CT detection and in disease-free smokers enrolled in the screening trial, resulted in the generation of miRNA signatures with strong predictive, diagnostic, and prognostic potential (area under the ROC curve ≥ 0.85). These signatures were validated in an independent cohort from a second randomized spiral-CT trial. These results indicate a role for miRNAs in lung tissues and plasma as molecular predictors of lung cancer development and aggressiveness and have theoretical and clinical implication for lung cancer management.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.1100048108

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Among the miRNA biomarkers examined, variation attributable to blood cell effects was greater in magnitude than many differences reported between cancer patients and controls.

    “we observed variation attributable to blood cell effects that was greater in magnitude than many of the differences reported between cancer patients and controls (13, 15, 20).”

    From Blood Cell Origin of Circulating MicroRNAs: A Cautionary Note for Cancer Biomarker Studies (2012) · cites this paper as [13]

  • A recent study found that increased ratios of neutrophil-expressed plasma miRNAs compared to RBC-expressed miRNAs were associated with poorer outcomes in non-small cell lung cancer patients.

    “A recent study published in PNAS found that increased ratios of neutrophil-expressed plasma miRNAs (miR-197, miR-142-3p, miR-140-5p, miR-17, miR-21) compared to RBC-expressed miRNAs (miR-92a, miR-486-5p, miR-16, and miR-451) were associated with poorer outcomes in non-small cell lung cancer patients (13).”

    From Blood Cell Origin of Circulating MicroRNAs: A Cautionary Note for Cancer Biomarker Studies (2012) · cites this paper as [13]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 37

  1. [1]Fontana RS, et al. Lung cancer screening: the Mayo program. J Occup Med. 1986;28:746–750. doi: 10.1097/00043764-198608000-00038. [DOI] [PubMed] [Google Scholar] · DOI
  2. [2]Bach PB, et al. Computed tomography screening and lung cancer outcomes. JAMA. 2007;297:953–961. doi: 10.1001/jama.297.9.953. [DOI] [PubMed] [Google Scholar] · DOI
  3. [3]Infante M, et al. DANTE Study Group. A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial. Am J Respir Crit Care Med. 2009;180:445–453. doi: 10.1164/rccm.200901-0076OC. [DOI] [PubMed] [Google Scholar] · DOI
  4. [4]Pastorino U. Lung cancer screening. Br J Cancer. 2010;102:1681–1686. doi: 10.1038/sj.bjc.6605660. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  5. [5]Bach PB. Is our natural-history model of lung cancer wrong? Lancet Oncol. 2008;9:693–697. doi: 10.1016/S1470-2045(08)70176-1. [DOI] [PubMed] [Google Scholar] · DOI
  6. [6]Chirieac LR, Flieder DB. High-resolution computed tomography screening for lung cancer: unexpected findings and new controversies regarding adenocarcinogenesis. Arch Pathol Lab Med. 2010;134:41–48. doi: 10.5858/134.1.41. [DOI] [PubMed] [Google Scholar] · DOI
  7. [7]Esquela-Kerscher A, Slack FJ. Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–269. doi: 10.1038/nrc1840. [DOI] [PubMed] [Google Scholar] · DOI
  8. [8]Mitchell PS, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA. 2008;105:10513–10518. doi: 10.1073/pnas.0804549105. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  9. [9]Ng EK, et al. Differential expression of microRNAs in plasma of colorectal cancer patients: A potential marker for colorectal cancer screening. Gut. 2009;58:1375–1381. doi: 10.1136/gut.2008.167817. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  10. [11]Hu Z, 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. 2010;28:1721–1726. doi: 10.1200/JCO.2009.24.9342. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  11. [12]Pastorino U, et al. Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results. Lancet. 2003;362:593–597. doi: 10.1016/S0140-6736(03)14188-8. [DOI] [PubMed] [Google Scholar] · DOI
  12. [13]Mestdagh P, et al. A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol. 2009;10:R64. doi: 10.1186/gb-2009-10-6-r64. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  13. [14]Sozzi G, et al. Effects of prolonged storage of whole plasma or isolated plasma DNA on the results of circulating DNA quantification assays. J Natl Cancer Inst. 2005;97:1848–1850. doi: 10.1093/jnci/dji432. [DOI] [PubMed] [Google Scholar] · DOI
  14. [15]Yanaihara N, et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9:189–198. doi: 10.1016/j.ccr.2006.01.025. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  15. [16]Patnaik SK, Kannisto E, Knudsen S, Yendamuri S. Evaluation of microRNA expression profiles that may predict recurrence of localized stage I non-small cell lung cancer after surgical resection. Cancer Res. 2010;70:36–45. doi: 10.1158/0008-5472.CAN-09-3153. [DOI] [PubMed] [Google Scholar] · DOI
  16. [17]Landi MT, et al. MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin Cancer Res. 2010;16:430–441. doi: 10.1158/1078-0432.CCR-09-1736. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  17. [18]Zhang JG, et al. MicroRNA-21 (miR-21) represses tumor suppressor PTEN and promotes growth and invasion in non-small cell lung cancer (NSCLC) Clin Chim Acta. 2010;411:846–852. doi: 10.1016/j.cca.2010.02.074. [DOI] [PubMed] [Google Scholar] · DOI
  18. [19]Qian S, et al. MicroRNA expression profile of bronchioalveolar stem cells from mouse lung. Biochem Biophys Res Commun. 2008;377:668–673. doi: 10.1016/j.bbrc.2008.10.052. [DOI] [PubMed] [Google Scholar] · DOI
  19. [20]Lebanony D, et al. Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma. J Clin Oncol. 2009;27:2030–2037. doi: 10.1200/JCO.2008.19.4134. [DOI] [PubMed] [Google Scholar] · DOI
  20. [22]Bishop JA, et al. Accurate classification of non-small cell lung carcinoma using a novel microRNA-based approach. Clin Cancer Res. 2010;16:610–619. doi: 10.1158/1078-0432.CCR-09-2638. [DOI] [PubMed] [Google Scholar] · DOI
  21. [23]Ueda R, et al. Dicer-regulated microRNAs 222 and 339 promote resistance of cancer cells to cytotoxic T-lymphocytes by down-regulation of ICAM-1. Proc Natl Acad Sci USA. 2009;106:10746–10751. doi: 10.1073/pnas.0811817106. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  22. [24]Masri S, et al. The role of microRNA-128a in regulating TGFbeta signaling in letrozole-resistant breast cancer cells. Breast Cancer Res Treat. 2010;124:89–99. doi: 10.1007/s10549-009-0716-3. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  23. [25]Myatt SS, et al. Definition of microRNAs that repress expression of the tumor suppressor gene FOXO1 in endometrial cancer. Cancer Res. 2010;70:367–377. doi: 10.1158/0008-5472.CAN-09-1891. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  24. [26]Fish JE, et al. miR-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15:272–284. doi: 10.1016/j.devcel.2008.07.008. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  25. [27]Polikepahad S, et al. Pro-inflammatory role for let-7 microRNAs in experimental asthma. J Biol Chem. 2010;285:30139–30149. doi: 10.1074/jbc.M110.145698. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  26. [28]Wong QW, et al. MiR-222 overexpression confers cell migratory advantages in hepatocellular carcinoma through enhancing AKT signaling. Clin Cancer Res. 2010;16:867–875. doi: 10.1158/1078-0432.CCR-09-1840. [DOI] [PubMed] [Google Scholar] · DOI
  27. [29]Duisters RF, et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res. 2009;104:170–178. doi: 10.1161/CIRCRESAHA.108.182535. [DOI] [PubMed] [Google Scholar] · DOI
  28. [30]Mott JL, Kobayashi S, Bronk SF, Gores GJ. mir-29 regulates Mcl-1 protein expression and apoptosis. Oncogene. 2007;26:6133–6140. doi: 10.1038/sj.onc.1210436. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  29. [31]Corney DC, Flesken-Nikitin A, Godwin AK, Wang W, Nikitin AY. MicroRNA-34b and MicroRNA-34c are targets of p53 and cooperate in control of cell proliferation and adhesion-independent growth. Cancer Res. 2007;67:8433–8438. doi: 10.1158/0008-5472.CAN-07-1585. [DOI] [PubMed] [Google Scholar] · DOI
  30. [32]Hackl M, et al. miR-17, miR-19b, miR-20a, and miR-106a are down-regulated in human aging. Aging Cell. 2010;9:291–296. doi: 10.1111/j.1474-9726.2010.00549.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  31. [33]Duncavage E, Goodgame B, Sezhiyan A, Govindan R, Pfeifer J. Use of microRNA expression levels to predict outcomes in resected stage I non-small cell lung cancer. J Thorac Oncol. 2010;5:1755–1763. doi: 10.1097/JTO.0b013e3181f3909d. [DOI] [PubMed] [Google Scholar] · DOI
  32. [34]Garofalo M, et al. miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation. Cancer Cell. 2009;16:498–509. doi: 10.1016/j.ccr.2009.10.014. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted] · DOI
  33. [35]Matsubara H, et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 2007;26:6099–6105. doi: 10.1038/sj.onc.1210425. [DOI] [PubMed] [Google Scholar] · DOI
  34. [36]Osada H, Takahashi T. let-7 and miR-17-92: small-sized major players in lung cancer development. Cancer Sci. 2011;102:9–17. doi: 10.1111/j.1349-7006.2010.01707.x. [DOI] [PubMed] [Google Scholar] · DOI
  35. [37]Du L, et al. miR-93, miR-98, and miR-197 regulate expression of tumor suppressor gene FUS1. Mol Cancer Res. 2009;7:1234–1243. doi: 10.1158/1541-7786.MCR-08-0507. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  36. [38]Shen J, et al. Plasma microRNAs as potential biomarkers for non-small-cell lung cancer. Lab Invest. November 29, 2010 doi: 10.1038/labinvest.2010.194. 10.1038/labinvest.2010.194. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  37. [39]Pastorino U, et al. Fluorodeoxyglucose uptake measured by positron emission tomography and standardized uptake value predicts long-term survival of CT screening detected lung cancer in heavy smokers. J Thorac Oncol. 2009;4:1352–1356. doi: 10.1097/JTO.0b013e3181bbf1dc. [DOI] [PubMed] [Google Scholar] · DOI

Cited by

Sorted by citations

Authors
Boeri, M., Verri, C., Conte, D., Roz, L., Modena, P., Facchinetti, F., Calabrò, E., Croce, C. M., Pastorino, U., & Sozzi, G.
Affiliations
  • Tumor Genomics Unit, Department of Experimental Oncology and Molecular Medicine, and
  • Unit of Experimental Oncology 1, Centro di Riferimento Oncologico, 33081 Aviano (PN), Italy; and
  • Unit of Thoracic Surgery, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy;
  • Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH 43210
Venue
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Published
2011-02-07
Volume
108
Issue
9
Pages
3713-3718
ISSN
  • 0027-8424
  • 1091-6490
DOI
10.1073/pnas.1100048108
Cited by
605
References
2
Language
en

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review