Ribonucleotide reductase large subunit M1 predicts poor survival due to modulation of proliferative and invasive ability of gastric cancer.
Ribonucleotide reductase large subunit M1 predicts poor survival due to modulation of proliferative and invasive ability of gastric cancer.
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DOI：
10.1371/journal.pone.0070191
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yen Y
中科院分区：
文献类型：
--
作者：
Wang Q;Liu X;Zhou J;Huang Y;Zhang S;Shen J;Loera S;Yuan X;Chen W;Jin M;Shibata S;Liu Y;Chu P;Wang L;Yen Y
我们的目的是探讨RRM 1在胃癌患者中的预后价值。研究对象为来自City of Hope（COH）和浙江大学（ZJU）的389例胃癌患者，其中67例有临床病理资料和生存资料。 RRM 1蛋白表达通过免疫组织化学在FFPE组织样品上测定。Kaplan-Meier和考克斯分析用于测量生存率。Ras/Raf活性和侵袭实验用于评估RRM 1在GC细胞系中的作用。 体外实验表明RRM 1激活Ras/Raf/MAPK信号转导通路，促进胃癌细胞增殖。RRM 1的表达与淋巴结转移、肿瘤大小、Ki 67表达、组织学类型和组织学分级有关（p<0.05）。Kaplan-Meier分析表明，高RRM 1表达预测了COH和ZJU队列中GC患者的较差生存率（对数秩p<0.01）。在多变量考克斯分析中，COH和ZJU组中RRM 1对总生存期的风险比分别为2.55（95%CI 1.27-5.15）和1.51（95%CI 1.07-2.13）。特别是，RRM 1特异性预测分化差和增殖能力高的晚期GC的结果。siRNA抑制RRM 1后，AGS和NCI-N87细胞的dNTP库、Ras/Raf和MMP-9活性以及p-MEK、p-ERK和NF-κB水平显著降低，导致细胞生长迟缓和侵袭能力降低。RRM 1过表达预示晚期TNM胃癌患者生存率低RRM 1有可能作为胃癌的预后生物标志物和治疗靶点。
We aimed to investigate the prognostic value of RRM1 in GC patients. A total of assessable 389 GC patients with clinicopathological and survival information were enrolled from City of Hope (COH, n = 67) and Zhejiang University (ZJU, n = 322). RRM1 protein expression was determined by immunohistochemistry on FFPE tissue samples. Kaplan-Meier and Cox analyses were used to measure survival. Ras/Raf activity and invasion assays were used to evaluate the role of RRM1 in GC cell lines. In vitro experiments demonstrated RRM1 activated Ras/Raf/MAPK signal transduction and promoted GC cell proliferation. Meanwhile, RRM1 expression was significantly associated with lymph node involvement, tumor size, Ki67 expression, histological subtype and histological grade in the GC tissue samples (p<0.05). Kaplan-Meier analysis illustrated that high RRM1 expression predicted poor survival in GC patients in the COH and ZJU cohorts (log-rank p<0.01). In multivariate Cox analysis, the hazard ratios of RRM1 for overall survival were 2.55 (95% CI 1.27–5.15) and 1.51 (95% CI 1.07–2.13) in the COH and ZJU sets, respectively. In particular, RRM1 specifically predicted the outcome of advanced GCs with poor differentiation and high proliferative ability. Furthermore, inhibition of RRM1 by siRNA significantly reduced the dNTP pool, Ras/Raf and MMP-9 activities and the levels of p-MEK, p-ERK and NF-κB, resulting in growth retardation and reduced invasion in AGS and NCI-N87 cells. RRM1 overexpression predicts poor survival in GC patients with advanced TNM stage. RRM1 could potentially serve as prognostic biomarker and therapeutic target for GCs.
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核糖核苷酸还原酶小亚基M2B预测结直肠癌的生存更好。
影响因子：
11.2
作者：
Liu X;Lai L;Wang X;Xue L;Leora S;Wu J;Hu S;Zhang K;Kuo ML;Zhou L;Zhang H;Wang Y;Wang Y;Zhou B;Nelson RA;Zheng S;Zhang S;Chu P;Yen Y
通讯作者：
Yen Y
影响因子：
5.2
作者：
Kurata, Nobuaki;Fujta, Hayato;Tanaka, Masao
通讯作者：
Tanaka, Masao
DOI：
10.1073/pnas.94.24.13181
发表时间：
1997-11-25
影响因子：
11.1
作者：
Fan, HZ;Huang, AP;Wright, JA
通讯作者：
Wright, JA
DOI：
10.1016/s0140-6736(09)60617-6
发表时间：
2009-08-08
期刊：
Lancet (London, England)
影响因子：
--
作者：
Hartgrink HH;Jansen EP;van Grieken NC;van de Velde CJ
通讯作者：
van de Velde CJ
影响因子：
7.4
作者：
通讯作者：
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