Integrating contextual miRNA and protein signatures for diagnostic and treatment decisions in cancer

Expert Review of Molecular Diagnostics

Volumn 11, Issue 8, 2011, Pages 813-827

  Sempere, Lorenzo F ^a  

^a NORRIS COTTON CANCER CENTER   (United States)

Author keywords

biomarkers; breast cancer; colorectal cancer; expression profiling; immunohistochemistry; in situ hybridization; lung cancer; miRNA; multiplexing; proteins; quantitative reverse transcriptase polymerase chain reaction

Indexed keywords

BEVACIZUMAB; BIOLOGICAL MARKER; CETUXIMAB; ERLOTINIB; GEFITINIB; MICRORNA; PANITUMUMAB; TAMOXIFEN;

BREAST CANCER; CANCER DIAGNOSIS; CANCER PATIENT; CANCER THERAPY; CLINICAL PRACTICE; COLORECTAL CANCER; COST EFFECTIVENESS ANALYSIS; DECISION MAKING; DIAGNOSTIC ACCURACY; HUMAN; LUNG CANCER; PROGNOSIS; REVIEW; SOLID TUMOR;

BREAST NEOPLASMS; COLORECTAL NEOPLASMS; FEMALE; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; INDIVIDUALIZED MEDICINE; LUNG NEOPLASMS; MICRORNAS; NEOPLASMS; PROTEINS; TUMOR MARKERS, BIOLOGICAL;

EID: 80054913521     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/erm.11.69     Document Type: Review

References (170)

1. Kochanek KD, Xu J, Murphy SL, Miniño AM, Kung H-S. Deaths: preliminary data for 2009. National Vital Statistics Reports 59 No. 4, Division of Vital Statistics, National Center for Health Statistics, MD, USA, 1-51 (2011).
2. Haber DA, Gray NS, Baselga J. The evolving war on cancer. Cell 145, 19-24 (2011).
3. Caskey CT. Using genetic diagnosis to determine individual therapeutic utility. Annu. Rev. Med. 61, 1-15 (2010).
4. Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294, 858-862 (2001).
5. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science 294, 853-858 (2001).
6. Lee RC, Ambros V. An extensive class of small RNAs in Caenorhabditis elegans. Science 294, 862-864 (2001).
7. Reinhart BJ, Slack FJ, Basson M et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403, 901-906 (2000).
8. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843-854 (1993).
9. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell 75, 855-862 (1993).
10. Ambros V. The functions of animal microRNAs. Nature 431, 350-355 (2004).
11. Bartel DP, Chen CZ. Micromanagers of gene expression: the potentially widespread influence of metazoan microRNAs. Nat. Rev. Genet. 5, 396-400 (2004).
12. Sempere LF, Kauppinen S. Translational implications of microRNAs in clinical diagnostics and therapeutics. In: Handbook of Cell Signaling. Bradshaw RA, Dennis EA (Eds). Academic Press, Oxford, UK, 2965-2981 (2009).
13. Ventura A, Jacks T. MicroRNAs and cancer: short RNAs go a long way. Cell 136, 586-591 (2009).
14. Garzon R, Marcucci G, Croce CM. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat. Rev. Drug Discov. 9, 775-789 (2010).
15. De SE, Ferretti E, Gulino A. MicroRNAs as biomarkers for CNS cancer and other disorders. Brain Res. 1338, 100-111 (2010).
16. Saba R, Schratt GM. MicroRNAs in neuronal development, function and dysfunction. Brain Res. 1338, 3-13 (2010).
17. Ketting RF. MicroRNA biogenesis and function: an overview. Adv. Exp. Med. Biol. 700, 1-14 (2011).
18. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat. Rev. Genet. 11, 597-610 (2010).
19. Bentwich I, Avniel A, Karov Y et al. Identification of hundreds of conserved and nonconserved human microRNAs. Nat. Genet. 37, 766-770 (2005).
20. Lim LP, Lau NC, Garrett-Engele P et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433, 769-773 (2005).
21. Selbach M, Schwanhausser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N. Widespread changes in protein synthesis induced by microRNAs. Nature 455, 58-63 (2008).
22. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature 455, 64-71 (2008).
23. Kozomara A, Griffiths-Jones S. miRBase: integrating microRNA annotation and deep-sequencing data. Nucleic Acids Res. 39, D152-D157 (2011).
24. Ferracin M, Veronese A, Negrini M. Micromarkers: miRNAs in cancer diagnosis and prognosis. Expert. Rev. Mol. Diagn. 10(3), 297-308 (2010).
25. Elmen J, Lindow M, Silahtaroglu A et al. Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver. Nucleic Acids Res. 36, 1153-1162 (2008).
26. Elmen J, Lindow M, Schutz S et al. LNA-mediated microRNA silencing in non-human primates. Nature 452, 896-899 (2008).
27. Trang P, Wiggins JF, Daige CL et al. Systemic delivery of tumor suppressor microRNA mimics using a neutral lipid emulsion inhibits lung tumors in mice. Mol. Ther. 19(6), 1116-1122 (2011).
28. Wiggins JF, Ruffino L, Kelnar K et al. Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34. Cancer Res. 70, 5923-5930 (2010).
29. Trang P, Medina PP, Wiggins JF et al. Regression of murine lung tumors by the let-7 microRNA. Oncogene 29, 1580-1587 (2010).
30. Ma L, Reinhardt F, Pan E et al. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat. Biotechnol. 28, 341-347 (2010).
31. Szafranska-Schwarzbach AE, Adai AT, Lee LS, Conwell DL, Andruss BF. Development of a miRNA-based diagnostic assay for pancreatic ductal adenocarcinoma. Expert. Rev. Mol. Diagn. 11, 249-257 (2011). Describes the development and validation of the first commercialized miRNA-based laboratory-developed test for the differential diagnosis of pancreatic ductal adenocarcinoma.
32. Matos LL, Trufelli DC, de Matos MG, da Silva Pinhal MA. Immunohistochemistry as an important tool in biomarkers detection and clinical practice. Biomark. Insights 5, 9-20 (2010).
33. Brennan DJ, O'Connor DP, Rexhepaj E, Ponten F, Gallagher WM. Antibody-based proteomics: fast-tracking molecular diagnostics in oncology. Nat. Rev. Cancer 10, 605-617 (2010).
34. Tholouli E, Sweeney E, Barrow E, Clay V, Hoyland JA, Byers RJ. Quantum dots light up pathology. J. Pathol. 216, 275-285 (2008).
35. Al-Janabi S, Huisman A, Van Diest PJ. Digital pathology: current status and future perspectives. Histopathology DOI: 10.1111/j.1365-2559.2011.03814.x (2011) (Epub ahead of print).
36. Chen X, Zheng B, Liu H. Optical and digital microscopic imaging techniques and applications in pathology. Anal. Cell Pathol. 34, 5-18 (2011).
37. Schwanhausser B, Busse D, Li N et al. Global quantification of mammalian gene expression control. Nature 473, 337-342 (2011).
38. Kauppinen S, Vester B, Wengel J. Locked nucleic acid: high-affinity targeting of complementary RNA for RNomics. Handb. Exp. Pharmacol. 405-422 (2006).
39. Nelson PT, Baldwin DA, Kloosterman WP, Kauppinen S, Plasterk RH, Mourelatos Z. RAKE and LNA-ISH reveal microRNA expression and localization in archival human brain. RNA 12, 187-191 (2006). First study on archived brain tissues that demonstrates the technical feasibility of detecting miRNAs by in situ hybridization (ISH) on formalin-fixed paraffin-embedded (FFPE) samples. This study also uncovers neuronal and glial cell-specific expression of some miRNAs as the basis of their differential expression in oligodendrogliomas, rather than deregulation within the cancer cells.
40. Sempere LF, Christensen M, Silahtaroglu A et al. Altered microRNA expression confined to specific epithelial cell subpopulations in breast cancer. Cancer Res. 67, 11612-11620 (2007). First study on breast cancer that uses a fluorescence-based ISH assay to identify epithelial cell expression of cancerassociated miRNAs on FFPE tissue specimens. This study is also the first to analyze miRNA by ISH on a tissue microarray (n = 100) and to uncover by these means the potential clinical utility of myoepithelial cell-expressed miRNAs.
41. Yamamichi N, Shimomura R, Inada K et al. Locked nucleic acid in situ hybridization analysis of miR-21 expression during colorectal cancer development. Clin. Cancer Res. 15, 4009-4016 (2009).
42. Liu X, Sempere LF, Ouyang H et al. MicroRNA-31 functions as an oncogenic microRNA in mouse and human lung cancer cells by repressing specific tumor suppressors. J. Clin. Invest. 120, 1298-1309 (2010).
43. Dillhoff M, Liu J, Frankel W, Croce C, Bloomston M. MicroRNA-21 is overexpressed in pancreatic cancer and a potential predictor of survival. J. Gastrointest. Surg. 12, 2171-2176 (2008).
44. Habbe N, Koorstra JB, Mendell JT et al. MicroRNA miR-155 is a biomarker of early pancreatic neoplasia. Cancer Biol. Ther. 8, 340-346 (2009).
45. Preis M, Gardner TB, Gordon SR et al. microRNA-10b expression correlates with response to neoadjuvant therapy and survival in pancreatic ductal adenocarcinoma. Clin. Cancer Res. 17, 5812-5821 (2011). First clinical study on endoscopic ultrasonography-guided fine-needle aspirate samples (n = 106) that uses a multiplex ISH/immunohistochemistry assay to uncover the potential applications of miR-10b as a novel diagnostic and prognostic biomarker in pancreatic adenocarcinoma.
46. Schneider M, Andersen DC, Silahtaroglu A et al. Cell-specific detection of microRNA expression during cardiomyogenesis by combined in situ hybridization and immunohistochemistry. J. Mol. Histol. 42, 289-299 (2011).
47. Donnem T, Eklo K, Berg T et al. Prognostic impact of miR-155 in non-small cell lung cancer evaluated by in situ hybridization. J. Transl. Med. 9, 6 (2011).
48. Gupta A, Mo YY. Detection of microRNAs in cultured cells and paraffin-embedded tissue specimens by in situ hybridization. Methods Mol. Biol. 676, 73-83 (2011).
49. Nelson PT, Dimayuga J, Wilfred BR. MicroRNA in situ hybridization in the human entorhinal and transentorhinal cortex. Front. Hum. Neurosci. 4, 7 (2010).
50. Schepeler T, Reinert JT, Ostenfeld MS et al. Diagnostic and prognostic microRNAs in stage II colon cancer. Cancer Res. 68, 6416-6424 (2008).
51. Nielsen BS, Jorgensen S, Fog JU et al. High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients. Clin. Exp. Metastasis 28, 27-38 (2011). First ISH-based study to use computerassisted image analysis to quantitate miR-21 expression on stromal cells and correlate different levels of stromal cell-specific expression with outcome in patients afflicted with colorectal cancer.
52. Sempere LF, Preis M, Yezefski T et al. Fluorescence-based codetection with protein markers reveals distinct cellular compartments for altered microRNA expression in solid tumors. Clin. Cancer Res. 16, 4246-4255 (2010). The first study to describe the technical feasibility of codetecting multiple miRNA and protein markers on the same FFPE tissue section. The use of a cell type-specific protein marker aids the analysis of miRNA expression and the identification of different cell type-specific expression patterns in the tumor microenvironment.
53. Nelson PT, Wilfred BR. In situ hybridization is a necessary experimental complement to microRNA (miRNA) expression profiling in the human brain. Neurosci. Lett. 466, 69-72 (2009).
54. Speel EJ, Hopman AH, Komminoth P. Tyramide signal amplification for DNA and mRNA in situ hybridization. Methods Mol. Biol. 326, 33-60 (2006).
55. Sempere LF, Korc M. Fully-automated multi-color co-detection of microRNA and protein biomarkers on formalin-fixed paraffin-embedded specimens of solid tumors. Presented at: 36th Annual National Society for Histotechnology Symposium/ Convention. Seattle, WA, USA, 24-29 September 2010.
56. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J. Clin. 60, 277-300 (2010).
57. Perou CM, Sorlie T, Eisen MB et al. Molecular portraits of human breast tumours. Nature 406, 747-752 (2000).
58. Sorlie T, Perou CM, Tibshirani R et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA 98, 10869-10874 (2001).
59. Sorlie T. Molecular portraits of breast cancer: tumour subtypes as distinct disease entities. Eur. J. Cancer 40, 2667-2675 (2004).
60. Sims AH, Ong KR, Clarke RB, Howell A. High-throughput genomic technology in research and clinical management of breast cancer. Exploiting the potential of gene expression profiling: is it ready for the clinic? Breast Cancer Res. 8, 214 (2006).
61. Carey LA, Perou CM, Livasy CA et al. Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295, 2492-2502 (2006).
62. Ross JS. Multigene classifiers, prognostic factors, and predictors of breast cancer clinical outcome. Adv. Anat. Pathol. 16, 204-215 (2009).
63. Overdevest JB, Theodorescu D, Lee JK. Utilizing the molecular gateway: the path to personalized cancer management. Clin. Chem. 55, 684-697 (2009).
64. Cheang MC, Voduc D, Bajdik C et al. Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin. Cancer Res. 14, 1368-1376 (2008).
65. Cheang MC, Chia SK, Voduc D et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J. Natl. Cancer Inst. 101, 736-750 (2009).
66. Paik S, Shak S, Tang G et al. A multigene assay to predict recurrence of tamoxifentreated, node-negative breast cancer. N. Engl. J. Med. 351, 2817-2826 (2004).
67. Weigelt B, Hu Z, He X et al. Molecular portraits and 70-gene prognosis signature are preserved throughout the metastatic process of breast cancer. Cancer Res. 65, 9155-9158 (2005).
68. Parker JS, Mullins M, Cheang MC et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J. Clin. Oncol. 27, 1160-1167 (2009).
69. DeNardo DG, Brennan DJ, Rexhepaj E et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Dis. DOI: 10.1158/2159-8274. CD-10-0028 (2011) (Epub ahead of print).
70. Planche A, Bacac M, Provero P et al. Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer. PLoS ONE 6, e18640 (2011).
71. Marchini C, Montani M, Konstantinidou G et al. Mesenchymal/ stromal gene expression signature relates to basal-like breast cancers, identifies bone metastasis and predicts resistance to therapies. PLoS ONE 5, e14131 (2010).
72. Sharma M, Beck AH, Webster JA et al. Analysis of stromal signatures in the tumor microenvironment of ductal carcinoma in situ. Breast Cancer Res. Treat. 123, 397-404 (2010).
73. Ma XJ, Dahiya S, Richardson E, Erlander M, Sgroi DC. Gene expression profiling of the tumor microenvironment during breast cancer progression. Breast Cancer Res. 11, R7 (2009).
74. Farmer P, Bonnefoi H, Anderle P et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat. Med. 15, 68-74 (2009).
75. Finak G, Bertos N, Pepin F et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat. Med. 14, 518-527 (2008).
76. Iorio MV, Ferracin M, Liu CG et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 65, 7065-7070 (2005).
77. Volinia S, Calin GA, Liu CG et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc. Natl Acad. Sci. USA 103, 2257-2261 (2006).
78. Andorfer CA, Necela BM, Thompson EA, Perez EA. MicroRNA signatures: clinical biomarkers for the diagnosis and treatment of breast cancer. Trends Mol. Med. 17, 313-319 (2011).
79. Le QJ, Caldas C. Micro-RNAs and breast cancer. Mol. Oncol. 4, 230-241 (2010).
80. Rothe F, Ignatiadis M, Chaboteaux C et al. Global MicroRNA expression profiling identifies miR-210 associated with tumor proliferation, invasion and poor clinical outcome in breast cancer. PLoS ONE 6, e20980 (2011). Serves to independently confirm prognostic utility of miR-210 in breast cancer. This study is also the first to do a head-to-head comparison of prognostic performance of a single miRNA-based versus a multi-mRNA signature-based assay.
81. Janssen EA, Slewa A, Gudlaugsson E et al. Biologic profiling of lymph node negative breast cancers by means of microRNA expression. Mod. Pathol. 23, 1567-1576 (2010).
82. Lowery AJ, Miller N, Devaney A et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 11, R27 (2009).
83. Blenkiron C, Goldstein LD, Thorne NP et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumour subtype. Genome Biol. 8, R214 (2007).
84. Mattie MD, Benz CC, Bowers J et al. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol. Cancer 5, 24 (2006).
85. Castellano L, Giamas G, Jacob J et al. The estrogen receptor-a-induced microRNA signature regulates itself and its transcriptional response. Proc. Natl Acad. Sci. USA 106, 15732-15737 (2009).
86. Yoshimoto N, Toyama T, Takahashi S et al. Distinct expressions of microRNAs that directly target estrogen receptor a in human breast cancer. Breast Cancer Res. Treat. 130(1), 331-339(2011).
87. Fu SW, Chen L, Man YG. miRNA biomarkers in breast cancer detection and management. J. Cancer 2, 116-122 (2011).
88. Foekens JA, Sieuwerts AM, Smid M et al. Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc. Natl Acad. Sci. USA 105, 13021-13026 (2008).
89. Camps C, Buffa FM, Colella S et al. hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin. Cancer Res. 14, 1340-1348 (2008).
90. Buffa FM, Camps C, Winchester L et al. microRNA associated progression pathways and potential therapeutic targets identified by integrated mRNA and microRNA expression profiling in breast cancer. Cancer Res. 71(17), 5635-5645 (2011).
91. Radojicic J, Zaravinos A, Vrekoussis T, Kafousi M, Spandidos DA, Stathopoulos EN. MicroRNA expression analysis in triple-negative (ER, PR and Her2/neu) breast cancer. Cell Cycle 10, 507-517 (2011).
92. Crosby ME, Kulshreshtha R, Ivan M, Glazer PM. MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 69, 1221-1229 (2009).
93. Vilar E, Gruber SB. Microsatellite instability in colorectal cancer-the stable evidence. Nat. Rev. Clin. Oncol. 7, 153-162 (2010).
94. Pino MS, Chung DC. Microsatellite instability in the management of colorectal cancer. Expert Rev. Gastroenterol. Hepatol. 5, 385-399 (2011).
95. Fearon ER. Molecular genetics of colorectal cancer. Annu. Rev. Pathol. 6, 479-507 (2011).
96. Mutch MG. Molecular profiling and risk stratification of adenocarcinoma of the colon. J. Surg. Oncol. 96, 693-703 (2007).
97. Salazar R, Roepman P, Capella G et al. Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. J. Clin. Oncol. 29, 17-24 (2011).
98. Luo X, Burwinkel B, Tao S, Brenner H. MicroRNA signatures: novel biomarker for colorectal cancer? Cancer Epidemiol. Biomarkers Prev. 20, 1272-1286 (2011).
99. Ma Y, Zhang P, Yang J, Liu Z, Yang Z, Qin H. Candidate microRNA biomarkers in human colorectal cancer: systematic review profiling studies and experimental validation. Int. J. Cancer DOI: 10.1002/ ijc.26232 (2011) (Epub ahead of print).
100. Lanza G, Ferracin M, Gafa R et al. mRNA/microRNA gene expression profile in microsatellite unstable colorectal cancer. Mol. Cancer 6, 54 (2007).
101. Kulda V, Pesta M, Topolcan O et al. Relevance of miR-21 and miR-143 expression in tissue samples of colorectal carcinoma and its liver metastases. Cancer Genet. Cytogenet. 200, 154-160 (2010).
102. Schetter AJ, Leung SY, Sohn JJ et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocarcinoma. JAMA 299, 425-436 (2008).
103. Shibuya H, Iinuma H, Shimada R, Horiuchi A, Watanabe T. Clinicopathological and prognostic value of microRNA-21 and microRNA-155 in colorectal cancer. Oncology 79, 313-320 (2010).
104. Yen LC, Uen YH, Wu DC et al. Activating KRAS mutations and overexpression of epidermal growth factor receptor as independent predictors in metastatic colorectal cancer patients treated with cetuximab. Ann. Surg. 251, 254-260 (2010).
105. Tol J, Punt CJ. Monoclonal antibodies in the treatment of metastatic colorectal cancer: a review. Clin. Ther. 32, 437-453 (2010).
106. Blanke CD, Goldberg RM, Grothey A et al. KRAS and colorectal cancer: ethical and pragmatic issues in effecting real-time change in oncology clinical trials and practice. Oncologist 16(8), 1061-1068 (2011).
107. Solmi R, Lauriola M, Francesconi M et al. Displayed correlation between gene expression profiles and submicroscopic alterations in response to cetuximab, gefitinib and EGF in human colon cancer cell lines. BMC Cancer 8, 227 (2008).
108. Ragusa M, Majorana A, Statello L et al. Specific alterations of microRNA transcriptome and global network structure in colorectal carcinoma after cetuximab treatment. Mol. Cancer Ther. 9, 3396-3409 (2010).
109. Zhang W, Winder T, Ning Y et al. A let-7 microRNA-binding site polymorphism in 3?-untranslated region of KRAS gene predicts response in wild-type KRAS patients with metastatic colorectal cancer treated with cetuximab monotherapy. Ann. Oncol. 22, 104-109 (2011).
110. Graziano F, Canestrari E, Loupakis F et al. Genetic modulation of the let-7 microRNA binding to KRAS 3′-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab- irinotecan. Pharmacogenomics J. 10, 458-464 (2010).
111. Wistuba II, Gazdar AF. Lung cancer preneoplasia. Annu. Rev. Pathol. 1, 331-348 (2006).
112. Bhattacharjee A, Richards WG, Staunton J et al. Classification of human lung carcinomas by mRNA expression profiling reveals distinct adenocarcinoma subclasses. Proc. Natl Acad. Sci. USA 98, 13790-13795 (2001).
113. Garber ME, Troyanskaya OG, Schluens K et al. Diversity of gene expression in adenocarcinoma of the lung. Proc. Natl Acad. Sci. USA 98, 13784-13789 (2001).
114. Yamagata N, Shyr Y, Yanagisawa K et al. A training-testing approach to the molecular classification of resected non-small cell lung cancer. Clin. Cancer Res. 9, 4695-4704 (2003).
115. Ring BZ, Seitz RS, Beck RA et al. A novel five-antibody immunohistochemical test for subclassification of lung carcinoma. Mod. Pathol. 22, 1032-1043 (2009).
116. Beer DG, Kardia SL, Huang CC et al. Gene-expression profiles predict survival of patients with lung adenocarcinoma. Nat. Med. 8, 816-824 (2002).
117. Powell CA, Spira A, Derti A et al. Gene expression in lung adenocarcinomas of smokers and nonsmokers. Am. J. Respir. Cell Mol. Biol. 29, 157-162 (2003).
118. Spira A, Beane JE, Shah V et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat. Med. 13, 361-366 (2007).
119. Subramanian J, Simon R. Gene expression-based prognostic signatures in lung cancer: ready for clinical use? J. Natl. Cancer Inst. 102, 464-474 (2010).
120. Lacroix L, Commo F, Soria JC. Gene expression profiling of non-small-cell lung cancer. Expert Rev. Mol. Diagn. 8, 167-178 (2008).
121. Roepman P, Jassem J, Smit EF et al. An immune response enriched 72-gene prognostic profile for early-stage non-smallcell lung cancer. Clin. Cancer Res. 15, 284-290 (2009).
122. Du L, Pertsemlidis A. MicroRNAs and lung cancer: tumors and 22-mers. Cancer Metastasis Rev. 29, 109-122 (2010).
123. Lin PY, Yu SL, Yang PC. MicroRNA in lung cancer. Br. J. Cancer 103, 1144-1148 (2010).
124. Yendamuri S, Kratzke R. MicroRNA biomarkers in lung cancer: MiRacle or quagMiRe? Transl. Res. 157, 209-215 (2011).
125. Landi MT, Zhao Y, Rotunno M et al. MicroRNA expression differentiates histology and predicts survival of lung cancer. Clin. Cancer Res. 16, 430-441 (2010).
126. Lebanony D, Benjamin H, Gilad S et al. Diagnostic assay based on hsa-miR-205 expression distinguishes squamous from nonsquamous non-small-cell lung carcinoma. J. Clin. Oncol. 27, 2030-2037 (2009).
127. Fassina A, Cappellesso R, Fassan M. Classification of non-small cell lung carcinoma in trans-thoracic needle specimens using microRNA expression profiling. Chest DOI: 10.1378/ chest.11-0708 (2011) (Epub ahead of print).
128. Del V, V, Cantaloni C, Cucino A et al. miR-205 expression levels in nonsmall cell lung cancer do not always distinguish adenocarcinomas from squamous cell carcinomas. Am. J. Surg. Pathol. 35, 268-275 (2011).
129. Xing L, Todd NW, Yu L, Fang H, Jiang F. Early detection of squamous cell lung cancer in sputum by a panel of microRNA markers. Mod. Pathol. 23, 1157-1164 (2010).
130. Bishop JA, Benjamin H, Cholakh H, Chajut A, Clark DP, Westra WH. Accurate classification of non-small cell lung carcinoma using a novel microRNAbased approach. Clin. Cancer Res. 16, 610-619 (2010).
131. Yanaihara N, Caplen N, Bowman E et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 9, 189-198 (2006).
132. Saito M, Schetter AJ, Mollerup S et al. The association of microRNA expression with prognosis and progression in early-stage, non-small cell lung adenocarcinoma: a retrospective analysis of three cohorts. Clin. Cancer Res. 17, 1875-1882 (2011).
133. Voortman J, Goto A, Mendiboure J et al. MicroRNA expression and clinical outcomes in patients treated with adjuvant chemotherapy after complete resection of non-small cell lung carcinoma. Cancer Res. 70, 8288-8298 (2010).
134. Fruh M. The search for improved systemic therapy of non-small cell lung cancer - what are today's options? Lung Cancer 72, 265-270 (2011).
135. Roberts PJ, Stinchcombe TE, Der CJ, Socinski MA. Personalized medicine in non-small-cell lung cancer: is KRAS a useful marker in selecting patients for epidermal growth factor receptor-targeted therapy? J. Clin. Oncol. 28, 4769-4777 (2010).
136. Read ML, Spice R, Parker AL, Mir S, Logan A. 12th Annual Congress of the European Society of Gene Therapy. Expert Opin. Biol. Ther. 5, 137-141 (2005).
137. Chin LJ, Ratner E, Leng S et al. A SNP in a let-7 microRNA complementary site in the KRAS 3′ untranslated region increases non-small cell lung cancer risk. Cancer Res. 68, 8535-8540 (2008).
138. Nelson HH, Christensen BC, Plaza SL, Wiencke JK, Marsit CJ, Kelsey KT. KRAS mutation, KRAS-LCS6 polymorphism, and non-small cell lung cancer. Lung Cancer 69, 51-53 (2010).
139. Weiss GJ, Bemis LT, Nakajima E et al. EGFR regulation by microRNA in lung cancer: correlation with clinical response and survival to gefitinib and EGFR expression in cell lines. Ann. Oncol. 19, 1053-1059 (2008).
140. Rai K, Takigawa N, Ito S et al. Liposomal delivery of microRNA-7- expressing plasmid overcomes epidermal growth factor receptor-tyrosine kinase inhibitor-resistance in lung cancer cells. Mol. Cancer Ther. 10(9), 1720-1727 (2011).
141. Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ. Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J. Biol. Chem. 284, 5731-5741 (2009).
142. Subramanian J, Simon R. What should physicians look for in evaluating prognostic gene-expression signatures? Nat. Rev. Clin. Oncol. 7, 327-334 (2010).
143. Xu JZ, Wong CW. Hunting for robust gene signature from cancer profiling data: sources of variability, different interpretations, and recent methodological developments. Cancer Lett. 296, 9-16 (2010).
144. Hu Z, Fan C, Oh DS et al. The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics 7, 96 (2006).
145. Lu J, Getz G, Miska EA et al. MicroRNA expression profiles classify human cancers. Nature 435, 834-838 (2005). The first high-throughput bead-based flow cytometric miRNA expression profiling study in a panel of multiple types of hematologic and solid cancers. This study uncovers specific miRNA signatures for each cancer type, which can facilitate diagnosis of cancer of unknown primary origin. This study also shows that miRNA-based assays can outperform mRNA-based assays in several diagnostic applications.
146. Ferracin M, Pedriali M, Veronese A et al. MicroRNA profiling for the identification of cancers with unknown primary tissue-of-origin. J. Pathol. 225(1), 43-45 (2011).
147. Varadhachary GR, Spector Y, Abbruzzese JL et al. Prospective gene signature study using microRNA to identify the tissue of origin in patients with carcinoma of unknown primary. Clin. Cancer Res. 17, 4063-4070 (2011).
148. Schwarzenbach H, Hoon DS, Pantel K. Cell-free nucleic acids as biomarkers in cancer patients. Nat. Rev. Cancer 11, 426-437 (2011).
149. Mostert B, Sieuwerts AM, Martens JW, Sleijfer S. Diagnostic applications of cell-free and circulating tumor cell-associated miRNAs in cancer patients. Expert Rev. Mol. Diagn. 11, 259-275 (2011).
150. Brase JC, Wuttig D, Kuner R, Sultmann H. Serum microRNAs as non-invasive biomarkers for cancer. Mol. Cancer 9, 306 (2010).
151. Scholer N, Langer C, Dohner H, Buske C, Kuchenbauer F. Serum microRNAs as a novel class of biomarkers: a comprehensive review of the literature. Exp. Hematol. 38, 1126-1130 (2010).
152. Hipp J, Cheng J, Hanson JC et al. SIVQ-aided laser capture microdissection: a tool for highthroughput expression profiling. J. Pathol. Inform. 2, 19 (2011).
153. Hanson JC, Tangrea MA, Kim S et al. Expression microdissection adapted to commercial laser dissection instruments. Nat. Protoc. 6, 457-467 (2011).
154. Kim MS, Kim T, Kong SY et al. Breast cancer diagnosis using a microfluidic multiplexed immunohistochemistry platform. PLoS. ONE 5, e10441 (2010). The first study that applies a multichambered microfluidics device to physically insulated different regions on a breast cancer tissue samples for parallel multiplex detection of diagnostic clinical protein markers. This strategy will enable researchers and clinicians to maximize the contextual information content that could be extracted from tissue specimens.
155. Rodriguez-Gonzalez FG, Sieuwerts AM, Smid M et al. MicroRNA-30c expression level is an independent predictor of clinical benefit of endocrine therapy in advanced estrogen receptor positive breast cancer. Breast Cancer Res. Treat. 127, 43-51 (2011).
156. Ota D, Mimori K, Yokobori T et al. Identification of recurrence-related microRNAs in the bone marrow of breast cancer patients. Int. J. Oncol. 38, 955-962 (2011).
157. Yu SL, Chen HY, Chang GC et al. MicroRNA signature predicts survival and relapse in lung cancer. Cancer Cell 13, 48-57 (2008).
158. Raponi M, Dossey L, Jatkoe T et al. MicroRNA classifiers for predicting prognosis of squamous cell lung cancer. Cancer Res. 69, 5776-5783 (2009).
159. Gong C, Yao Y, Wang Y et al. Up-regulation of miR-21 mediates resistance to trastuzumab therapy for breast cancer. J. Biol. Chem. 286, 19127-19137 (2011).
160. Qian B, Katsaros D, Lu L et al. High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-b1. Breast Cancer Res. Treat. 117, 131-140 (2009).
161. Yan LX, Huang XF, Shao Q et al. MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA 14, 2348-2360 (2008).
162. Drebber U, Lay M, Wedemeyer I et al. Altered levels of the onco-microRNA 21 and the tumor-supressor microRNAs 143 and 145 in advanced rectal cancer indicate successful neoadjuvant chemoradiotherapy. Int. J. Oncol. 39, 409-415 (2011).
163. Diaz R, Silva J, Garcia JM et al. Deregulated expression of miR-106a predicts survival in human colon cancer patients. Genes Chromosomes Cancer 47, 794-802 (2008).
164. Nishida N, Yokobori T, Mimori K et al. MicroRNA miR-125b is a prognostic marker in human colorectal cancer. Int. J. Oncol. 38, 1437-1443 (2011).
165. Takamizawa J, Konishi H, Yanagisawa K et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64, 3753-3756 (2004).
166. Markou A, Tsaroucha EG, Kaklamanis L, Fotinou M, Georgoulias V, Lianidou ES. Prognostic value of mature microRNA-21 and microRNA-205 overexpression in non-small cell lung cancer by quantitative real-time RT-PCR. Clin. Chem. 54, 1696-1704 (2008).
167. Gao W, Shen H, Liu L, Xu J, Xu J, Shu Y. miR-21 overexpression in human primary squamous cell lung carcinoma is associated with poor patient prognosis. J. Cancer Res. Clin. Oncol. 137, 557-566 (2011).
168. Gallardo E, Navarro A, Vinolas N et al. miR-34a as a prognostic marker of relapse in surgically resected non-small-cell lung cancer. Carcinogenesis 30, 1903-1909 (2009).
169. American Joint Committee on Cancer www.cancerstaging.org
170. The Gene Ontology www.geneontology.org