Specific peripheral miRNA profiles for distinguishing lung cancer from COPD.

Recently we reported differential miRNA signatures in blood cells of lung cancer patients and healthy controls. With the present study we wanted to investigate if miRNA blood signatures are also suited to differentiate lung cancer patients from COPD patients. We compared the expression of 863 human miRNAs in blood cells of lung cancer patients, COPD patients, and healthy controls. The miRNA pattern from patients with lung cancer and COPD were more similar to each other than to the healthy controls. However, we were able to discriminate lung cancer patients and COPD patients with 90.4% accuracy, 89.2% specificity, and 91.7% sensitivity. In total, 140 miRNAs were significant for the comparison COPD and controls, 61 miRNAs were significant for the comparison lung cancer and controls, and 14 miRNAs were significant for the comparison lung cancer and COPD. Screening target databases yielded over 400 putative targets for those 14 miRNAs. The predicted mRNA targets of three of the 14 miRNAs were significantly up-regulated in PBMCs of lung cancer patients compared to patients with non-malignant lung diseases. In conclusion, we showed that blood miRNA signatures are suitable to distinguish lung cancer from COPD.

[1]  V. Bronte,et al.  Tumor‐induced tolerance and immune suppression by myeloid derived suppressor cells , 2008, Immunological reviews.

[2]  X. Chen,et al.  Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases , 2008, Cell Research.

[3]  Ann M. Killary,et al.  MicroRNAs in Plasma of Pancreatic Ductal Adenocarcinoma Patients as Novel Blood-Based Biomarkers of Disease , 2009, Cancer Prevention Research.

[4]  Stijn van Dongen,et al.  miRBase: microRNA sequences, targets and gene nomenclature , 2005, Nucleic Acids Res..

[5]  M. Nishimura,et al.  Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin–cyclophosphamide chemotherapy , 2008, Cancer Immunology, Immunotherapy.

[6]  F. Slack,et al.  Oncomirs — microRNAs with a role in cancer , 2006, Nature Reviews Cancer.

[7]  F. Slack,et al.  A truth serum for cancer — microRNAs have major potential as cancer biomarkers , 2008, Cell Research.

[8]  George A. Calin,et al.  MicroRNA identification in plasma and serum: a new tool to diagnose and monitor diseases , 2009, Expert opinion on biological therapy.

[9]  I. Borrello,et al.  Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. , 2008, Cancer research.

[10]  J J Bax,et al.  COPD and cancer mortality: the influence of statins , 2009, Thorax.

[11]  Malik Yousef,et al.  Gene expression profiles in peripheral blood mononuclear cells can distinguish patients with non-small cell lung cancer from patients with nonmalignant lung disease. , 2009, Cancer research.

[12]  I. Jolliffe Principal Component Analysis , 2002 .

[13]  L. Hood,et al.  Circulating microRNAs, potential biomarkers for drug-induced liver injury , 2009, Proceedings of the National Academy of Sciences.

[14]  Robert Tibshirani,et al.  Fataluku medicinal ethnobotany and the East Timorese military resistance , 2007, Journal of ethnobiology and ethnomedicine.

[15]  H. Horvitz,et al.  MicroRNA expression profiles classify human cancers , 2005, Nature.

[16]  E. Miska,et al.  MicroRNA—implications for cancer , 2007, Virchows Archiv.

[17]  Christina Backes,et al.  A dictionary on microRNAs and their putative target pathways , 2010, Nucleic acids research.

[18]  P. Metcalf,et al.  COPD prevalence is increased in lung cancer, independent of age, sex and smoking history , 2009, European Respiratory Journal.

[19]  Iris Barshack,et al.  MicroRNA expression differentiates between primary lung tumors and metastases to the lung. , 2010, Pathology, research and practice.

[20]  S. Albelda,et al.  Cross-Talk between Myeloid-Derived Suppressor Cells and Macrophages Subverts Tumor Immunity toward a Type 2 Response1 , 2007, The Journal of Immunology.

[21]  Hans-Peter Lenhof,et al.  Multiple Sclerosis: MicroRNA Expression Profiles Accurately Differentiate Patients with Relapsing-Remitting Disease from Healthy Controls , 2009, PloS one.

[22]  Yariv Yogev,et al.  Serum MicroRNAs Are Promising Novel Biomarkers , 2008, PloS one.

[23]  J. Ferlay,et al.  Global Cancer Statistics, 2002 , 2005, CA: a cancer journal for clinicians.

[24]  Vladimir N. Vapnik,et al.  The Nature of Statistical Learning Theory , 2000, Statistics for Engineering and Information Science.

[25]  Y. Hochberg A sharper Bonferroni procedure for multiple tests of significance , 1988 .

[26]  Y. Benjamini,et al.  Controlling the false discovery rate in behavior genetics research , 2001, Behavioural Brain Research.

[27]  Michael Simoff,et al.  Impact of comorbidity on lung cancer survival , 2003, International journal of cancer.

[28]  Manuel Hidalgo,et al.  Disease-associated expression profiles in peripheral blood mononuclear cells from patients with advanced renal cell carcinoma. , 2003, Cancer research.

[29]  Sam Griffiths-Jones,et al.  miRBase: the microRNA sequence database. , 2006, Methods in molecular biology.

[30]  Manuel Hidalgo,et al.  Transcriptional profiles in peripheral blood mononuclear cells prognostic of clinical outcomes in patients with advanced renal cell carcinoma. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[31]  Christina Backes,et al.  GeneTrail—advanced gene set enrichment analysis , 2007, Nucleic Acids Res..

[32]  W. Roa,et al.  Identification of a new microRNA expression profile as a potential cancer screening tool. , 2010, Clinical and investigative medicine. Medecine clinique et experimentale.

[33]  Eckart Meese,et al.  miRNAs in lung cancer - Studying complex fingerprints in patient's blood cells by microarray experiments , 2009, BMC Cancer.

[34]  M. Thun,et al.  Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. , 2007, American journal of respiratory and critical care medicine.

[35]  A. Jemal,et al.  Global Cancer Statistics , 2011 .

[36]  Sonja Vorwerk,et al.  Microfluidic-based enzymatic on-chip labeling of miRNAs. , 2008, New biotechnology.

[37]  K. Zier,et al.  Resection of Solid Tumors Reverses T Cell Defects and Restores Protective Immunity1 , 2000, The Journal of Immunology.