title: Reduced expression of Dicer associated with poor prognosis in lung cancer patients.
abstract: Emerging evidence suggests that microRNA, which are well-conserved, abundant and small regulatory RNA, may be involved in the pathogenesis of human cancers. We recently reported that expression of let-7 was frequently reduced in lung cancers, and that reduced let-7 expression was significantly associated with shorter patient survival. Two members of the double-stranded RNA-specific endonuclease family, Dicer and Drosha, convert precursor forms of microRNA into their mature forms using a stepwise process. In the present study, we examined expression levels of these genes in 67 non-small cell lung cancer cases, and found for the first time that Dicer expression levels were reduced in a fraction of lung cancers with a significant prognostic impact on the survival of surgically treated cases. It should be noted that multivariate COX regression analysis showed that the prognostic impact of Dicer (P=0.001) appears to be independent of disease stage (P=0.001), while logistic regression analysis demonstrated that the higher incidence of reduced Dicer expression in poorly differentiated tumors remained significant even after correction for other parameters (P=0.02). Given the fundamental and multiple biological roles of Dicer in various cellular processes, our results suggest the involvement of reduced Dicer expression in the development of lung cancers, thus warranting further investigations of the underlying mechanisms, which can be expected to enhance understanding of the molecular pathogenesis of this fatal cancer.
authors.affiliation: Division of Molecular Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Karube
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Osada
authors.forename: Shuta
authors.initials: S
authors.lastname: Tomida
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tatematsu
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yanagisawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Junichi
authors.initials: J
authors.lastname: Takamizawa
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Miyoshi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
mesh_terms: D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D043244:Ribonuclease III / Q000235:genetics*; D012907:Smoking; D016019:Survival Analysis
chemical_list: D035683:MicroRNAs; C517918:DROSHA protein, human; D043244:Ribonuclease III
references.citation: Science. 2002 Sep 13;297(5588):1833-7
references.pmid: 12193640
references.citation: Mol Cancer Res. 2003 Oct;1(12):882-91
references.pmid: 14573789
references.citation: Nat Genet. 1994 Apr;6(4):332-3
references.pmid: 8054970
references.citation: Cell. 2003 Jun 13;113(6):673-6
references.pmid: 12809598
references.citation: Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16648-53
references.pmid: 12482946
references.citation: Cell. 2004 Jan 23;116(2):281-97
references.pmid: 14744438
references.citation: Genes Dev. 2002 Jan 1;16(1):6-21
references.pmid: 11782440
references.citation: Science. 2001 Aug 3;293(5531):834-8
references.pmid: 11452083
references.citation: Oncogene. 1998 Dec 10;17(23):3029-33
references.pmid: 9881705
references.citation: Genes Chromosomes Cancer. 1997 May;19(1):29-35
references.pmid: 9135992
references.citation: Cancer Res. 1993 May 15;53(10 Suppl):2393-8
references.pmid: 8485726
references.citation: Genes Chromosomes Cancer. 2000 Jul;28(3):337-41
references.pmid: 10862040
references.citation: Nature. 2001 Jan 18;409(6818):363-6
references.pmid: 11201747
references.citation: Oncogene. 1999 Jul 29;18(30):4295-300
references.pmid: 10439037
references.citation: EMBO J. 2002 Sep 2;21(17):4663-70
references.pmid: 12198168
references.citation: Am J Pathol. 2001 Oct;159(4):1345-52
references.pmid: 11583962
references.citation: Science. 2002 Sep 27;297(5590):2232-7
references.pmid: 12215653
references.citation: Science. 2001 Sep 21;293(5538):2269-71
references.pmid: 11486053
references.citation: J Cell Biol. 2002 Jan 7;156(1):17-21
references.pmid: 11781331
references.citation: Cancer Res. 2004 Jun 1;64(11):3753-6
references.pmid: 15172979
references.citation: Oncogene. 2002 Oct 21;21(48):7421-34
references.pmid: 12379883
references.citation: Oncogene. 1993 Mar;8(3):671-5
references.pmid: 8437850
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):193-8
references.pmid: 12509501
references.citation: Oncogene. 1995 Mar 16;10(6):1193-8
references.pmid: 7700644
references.citation: Cell. 2001 Jul 13;106(1):23-34
references.pmid: 11461699
references.citation: Cancer Res. 2001 Nov 15;61(22):8331-9
references.pmid: 11719467
references.citation: Chromosome Res. 2003;11(2):137-46
references.pmid: 12733640
references.citation: Oncogene. 2002 Oct 7;21(45):6884-97
references.pmid: 12362271
references.citation: Cancer Res. 1995 Aug 1;55(15):3246-9
references.pmid: 7614456
references.citation: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15524-9
references.pmid: 12434020
references.citation: Nature. 2003 Sep 25;425(6956):415-9
references.pmid: 14508493
references.citation: Cancer Res. 1989 Mar 1;49(5):1095-8
references.pmid: 2563671
references.citation: Cancer Res. 2002 Aug 1;62(15):4464-8
references.pmid: 12154056
references.citation: Genes Dev. 2001 Oct 15;15(20):2654-9
references.pmid: 11641272
references.citation: Cancer Res. 1994 Mar 1;54(5):1152-5
references.pmid: 8118797