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. 2005 Feb;96(2):111-5.
doi: 10.1111/j.1349-7006.2005.00015.x.

Reduced expression of Dicer associated with poor prognosis in lung cancer patients

Yoko Karube  1 , Hisaaki Tanaka, Hirotaka Osada, Shuta Tomida, Yoshio Tatematsu, Kiyoshi Yanagisawa, Yasushi Yatabe, Junichi Takamizawa, Shinichiro Miyoshi, Tetsuya Mitsudomi, Takashi Takahashi
Affiliations

Reduced expression of Dicer associated with poor prognosis in lung cancer patients

Yoko Karube et al. Cancer Sci. 2005 Feb.

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.

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Figures

Figure 1
Figure 1
Histograms of distributions of non‐small cell lung cancers (NSCLC) according to their expression of double‐stranded RNA‐specific endonucleases mRNA. (A) Scattered plot analysis of expression levels of Dicer and Drosha. (B) Histogram of Dicer expression level at log2 value in NSCLC. With the threshold set at −1.0 of log2 value, patients were divided into two groups: low, with Dicer log2 value expression <−1.0; and high, with Dicer log2 value expression = −1.0. (C) Histogram of Drosha log2 value expression level in NSCLC. With the threshold set at 1.1 of log2 value, patients were divided into two groups: low, with Drosha log2 value expression <1.1; and high, with Dicer log2 value expression = 1.1. X‐axis, log2 value; Y‐axis, number of cases.
Figure 2
Figure 2
Analysis of overall survival of patients with high or low expression of double‐stranded RNA‐specific endonucleases. (A) Kaplan‐Meier survival curves for lung cancer patients, who were classified as showing either high or low Dicer expression. Dicer status was found to be strongly associated (log‐rank, P = 0.0001) with patient survival. (B) Kaplan‐Meier survival curve for lung cancer patients, who were classified as showing either high or low Drosha expression. Drosha status did not show a significant (log‐rank, P = 0.06) relationship with patient survival. X‐axis, length of survival after surgery; Y‐axis, percentage of survivors.
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