TY - JOUR
T1 - Enhancer of zeste homolog 2 overexpression in nasopharyngeal carcinoma
T2 - An independent poor prognosticator that enhances cell growth
AU - Hwang, Chung Feng
AU - Huang, Hsuan Ying
AU - Chen, Chang Han
AU - Chien, Chih Yen
AU - Hsu, Yao Chung
AU - Li, Chien Feng
AU - Fang, Fu Min
PY - 2012/2/1
Y1 - 2012/2/1
N2 - Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median (≥60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.
AB - Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median (≥60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.
KW - EZH2
KW - Nasopharyngeal carcinoma
KW - Proliferation
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=84862956349&partnerID=8YFLogxK
U2 - 10.1016/j.ijrobp.2010.11.062
DO - 10.1016/j.ijrobp.2010.11.062
M3 - 文章
C2 - 21300475
AN - SCOPUS:84862956349
SN - 0360-3016
VL - 82
SP - 597
EP - 604
JO - International Journal of Radiation Oncology Biology Physics
JF - International Journal of Radiation Oncology Biology Physics
IS - 2
ER -
