21 4 2011 7 Journal of Jiangsu University Medicine Edition Vol. 21 No. 4 Jul. 2011 mirnalet7 C-myc 1 1 2 2 2 3 1. 224005 2. 224005 3. 215123 mirnalet7 let7 C-myc NSCLC let7 C-myc 68 NSCLC NSCLC 20 NSCLC Let7 NSCLC 39. 7% 75. 0% χ 2 = 6. 367 P < 0. 05 C-myc NSCLC 54. 4% 25. 0% χ 2 = 4. 245 P < 0. 05 Let7 C-myc P > 0. 05 let7 C-myc NSCLC r = - 0. 404 P < 0. 01 let7 2 χ 2 = 4. 84 P = 0. 027 8 Cmyc 2 χ 2 = 2. 47 P = 0. 116 4 Let7 C- myc NSCLC mirnalet7 C-myc R734. 2 A 1671-7783 2011 04-0344 - 05 Expression and clinical pathological significance of mirnalet7 C-myc in non-small cell lung cancer XU Chuan-hai 1 LAN Jian-yun 1 YAN Xiao-ou 2 SHEN Cheng-hong 2 YAN Xiao-mei 2 FENG Yi-zhong 3 1. Department of Pathology the First People's Hospital of Yancheng Yancheng Jiangsu 224005 2. Department of Oncology the First People' s Hospital of Yancheng Yancheng Jiangsu 224005 3. Department of Pathology and Physiopathology School of Medicine Soochow University Suzhou Jiangsu 215123 China Abstract Objective To study the effects of micrornalet7 C-myc on carcinogenesis and progression in non-small cell lung cancer NSCLC. Methods In-situ hybridization was applied to detect the expression of let7 in 68 cases of non-small cell lung cancer and 20 cases of adjacent lung tissues while SP immunohistochemistry was adopted to measure C-myc in these specimens. Results The positive rate of let7 in NSCLC group was 39. 7% which was lower than 75. 0% in control group χ 2 = 6. 367 P < 0. 05 while the positive rate of C-myc in NSCLC group was 54. 4% which was higher than 25. 0% in control group χ 2 = 4. 245 P < 0. 05. The positive rate of let7 and C-myc had no relation with clinic-pathological parameter P > 0. 05 there was an obvious negative correlation between let7 and C-myc r = - 0. 404 P < 0. 01. The 2-year survival rate of positive let7 is higher than that of the negative group χ 2 = 4. 84 P = 0. 027 8. There had no statistical significance between positive and negative groups of C-myc for two-year survival χ 2 = 2. 47 P = 0. 116 4. Conclusion The lower expression level of let7 and high expression level of C- myc were related with NSCLC and further research were needed. Key words non-small cell lung cancer micrornalet7 C-myc in-situ hybridization immunohistochemistry YK2009103 1975
4. mirnalet7 C-myc 345 1. 4 mirnalet7 - SP RNA 4 μm 2000 Reinhart 3% 10 min 1 mir- 10% 10 min 4 NAlet7 C-myc 68 NSCLC mirnalet7 C-myc 20 min SP 10 min DAB 3 3 NSCLC PBS NSCLC 1 1. 1 1. 5 2007 6 12 let7 C-myc NSCLC 68 NSCLC 5 cm 400 20 68 53 5 200 1 000 15 60 44 < 60 24 38 ~ 77 60 35 33 35 8 20 2 < 10% 0 10% ~ 25% 1 26% ~ 50% 2 51% ~ 75% 3 > 75% 4 0 23 25 15 10 1 2 3 3 cm 31 > 3 cm 37 = 25 < 3 3 ~ 6 43 44 24 2009 > 6 UICC 7 TNM TNMⅠ 37 TNMⅡ 19 TNMⅢ 12 1. 6 SPSS11. 0 2009 12 31 let7 C-myc NSCLC χ 2 let7 C-myc NSCLC Spearman let7 C-myc 1. 2 Kaplan-Meier Has-let-7a Exiqon C-myc Log-rank Invitrogen P < 0. 05 S-P DAB PBS 2 ISH 2. 1 mirnalet7 4% SABC-POD let7 NSCLC let7 1. 3 1 68 NSCLC 27 41 39. 7% mirna 1 400 42 15 5 75. 0% 16 h 37 χ 2 = 6. 367 P < 0. 05 Let7 60 min SABC DAB NSCLC
346 21 P > 0. 05 1 2. 2 C-myc NSCLC 5 25. 0% χ 2 = 4. 245 P < 0. 05 C-myc 2 C-myc NSCLC P > 0. 05 37 54. 4% 1 1 Tab 1 Let7 C-myc NSCLC Relationship between clinical pathological parameters and expression of mirnalet7 C-myc in non-small cell lung cancer n 60 44 19 43. 2 < 60 24 8 33. 3 53 20 37. 7 15 7 46. 7 44 21 47. 7 24 6 25. 0 > 3 cm 37 18 48. 6 3 cm 31 9 29. 0 35 11 31. 4 33 16 48. 5 25 6 24. 0 43 21 48. 8 25 12 48. 0 43 15 34. 9 P-TNM Ⅰ 37 12 32. 0 Ⅱ 19 9 47. 0 Ⅲ 12 6 50. 0 Let7 C-myc % χ 2 P % χ 2 P 0. 285 > 0. 05 0. 106 > 0. 05 2. 468 > 0. 05 1. 954 > 0. 05 1. 413 > 0. 05 3. 102 > 0. 05 0. 654 > 0. 05 1. 815 > 0. 05 21 47. 7 16 66. 7 28 52. 8 9 60. 0 21 47. 7 16 66. 7 16 43. 2 21 67. 7 17 48. 6 20 60. 6 10 40. 0 27 62. 8 15 60. 0 22 51. 2 17 46. 0 11 58. 0 10 83. 0 1. 547 > 0. 05 0. 039 > 0. 05 1. 547 > 0. 05 3. 153 > 0. 05 0. 566 > 0. 05 2. 455 > 0. 05 0. 205 > 0. 05 5. 181 > 0. 05 2. 3 let7 C-myc NSCLC Kaplan-Meier C-myc let7 42. 2% let7 Log-rank let7 70. 7% let7 2 r = - 0. 404 P < 0. 01 χ 2 = 4. 84 P = 0. 027 8 2. 4 let7 C-myc 2 let7 2 68 NSCLC 14 3 C-myc 2 54 NSCLC 4 C-myc 2 79. 4% 24. 18 2 χ 2 = 2. 47
4. mirnalet7 C-myc 347 P = 0. 116 4 3 Fig 3 2 let7 5 2007 Weidhaas 4 let7 let7 let7 let7 let7 2 Relationship between expression of let7 and 2-year survival rate let7 C-myc MC29 5 myc C-myc 20% C-myc 6 Zajac-Kaye 7 C-myc 4 C-myc 2 Fig 4 Relationship between expression of C-myc and 2-year survival rate 2006 Hsu 8 3 66 C-myc mirna 18 ~ 25 89. 4% C-myc RNA C-myc NSCLC mirnalet7 mirna Reinhart 1 P < 0. 05 2000 C. elegans TNM let7 2004 Takamizawa 3 P > 0. 05 let7 143 C-myc let7 COX C-myc let7 3'UTR let7 let7 A549 let7 2006 Akao 9 let7 let7 A549 myc 2009 Chang 10 C-myc let7 NSCLC myc mirna let7 let7 NSCLC let7 C-myc let7 let7 C-myc NSCLC let7 NSCLC NSCLC 2 P < 0. 05 let7 2 1 2
348 21 1 Reinhart BJ Slack FJ Basson M et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans J. Nature 2000 403 6772 901-906. 2 Kawasaki H Altieri DC Lu CD et al. Inhibition of apoptosis by surviving predicts shorter survival rates in colorectal cancer J. Cancer Res 1998 58 22 5071-5074. 3 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 J. Cancer Res 2004 64 11 3753-3756. 4 Weidhaas JB Babar I Nallur SM et a1. MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy J. Cancer Res 2007 67 23 11111-11116. 5 Dedieu JF Gazin C Rigolet M et al. Evolutionary conservation of the product of human C-myc exon I and its inducible expression in a murine cell line J. Oncogene 1988 3 5 523-529. 6 Nesbit CE Tersak JM Prochownik EV. MYC oncogenes and human neoplastic disease J. Oncogene 1999 18 19 3004-3016. 7 Zajac-Kaye M. Myc oncogene a key component in cell cycle regulation its implication for lung cancer J. Lung Cancer 2001 34 Suppl 2 43-46. 8 Hsu CP Hsu NY Lee LW et al. Est2 binding site single nucleotide polymorphism at the htert gene promotereffect on telomerase expression and telomere length maintenance in non-small cell lung cancer J. Eur J Cancer 2006 42 10 1466-1474. 9 Akao Y Nakagawa Y Naoe T. Let-7 microrna functions as a potential growth suppressor in human colon cancer eells J. Biol Pharm Bull 2006 29 5 903-906. 10 Chang TC Zeitels LR Hwang HW et al. Lin28B transactivation is necessary for Myc-mediated let7 repression and proliferation J. Proc Natl Acad Sci U S A 2009 106 9 3384-3389. 2011-04 - 25 343 2 Silver MA. The natriuretic peptide system kidney and cardiovascular effects J. Curr Opin Nephrol Hyper- BNP tens 2006 15 1 14-21 BNP 3 Krupicka J Janota T Kasalová Z et al. Natriuretic peptides-physiology pathophysiology and clinical use in heart failure J. Physiol Res 2009 58 2 171-177. 4 Chaudhary KR Batchu SN Das D et al. Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated BNP CKMB improved post-ischaemic recovery of heart contractile BNP function J. Cardiovasc Res 2009 83 2 362-370 1 5 Burley DS Hamid SA Baxter GF. Cardioprotective actions of peptide hormones in myocardial ischemia J. BNP Heart Fail Rev 2007 12 3 /4 279-291 6 Bonnet S Archer SL Allalunis-Tuener J et al. A mitochondria-k + channel axis is suppressed in cancer and its BNP 1 BNP 3 normalization promotes apoptosis and inhibits cancer LVEF 1 growth J. Cancer Cell 2007 11 1 37-51. BNP 7. B J. 2009 1. M. 2008 190-261. 37 8 716-720. 2011-04 - 26