The O-glycan pathway is associated with in vitro sensitivity to gemcitabine and overall survival from ovarian cancer.
The O-glycan pathway is associated with in vitro sensitivity to gemcitabine and overall survival from ovarian cancer.
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O-聚糖途径与对吉西他滨的体外敏感性以及卵巢癌的总生存率有关。
DOI：
10.3892/ijo.2012.1451
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发表时间：
2012-07
影响因子：
5.2
通讯作者：
Lancaster JM
中科院分区：
文献类型：
--
作者：
Bou Zgheib N;Xiong Y;Marchion DC;Bicaku E;Chon HS;Stickles XB;Sawah EA;Judson PL;Hakam A;Gonzalez-Bosquet J;Wenham RM;Apte SM;Cubitt CL;Chen DT;Lancaster JM
卵巢癌（Ovarian cancer，OVCA）是妇科最致命的恶性肿瘤。与这种疾病相关的高死亡率在很大程度上是由于对化疗产生耐药性;然而，其生物学基础尚不清楚。吉西他滨常用于治疗铂耐药OVCA患者。我们报告了与OVCA对吉西他滨反应相关的分子信号通路。对41个OVCA细胞系进行基因表达分析;同时，使用CellTiter-Blue活力测定定量吉西他滨的IC 50值。计算基因表达和吉西他滨IC 50值的Pearson相关系数。对与吉西他滨敏感性相关的基因进行通路分析。对于鉴定的途径，使用主成分分析来获得途径特征和相应的分数，其代表途径表达的总体测量。然后在来自142名III/IV期浆液性OVCA患者的一系列临床基因组数据集中评估所鉴定的途径的表达水平。我们发现体外吉西他滨敏感性与131个基因的表达相关（p<0.001）。这些基因包括三种分子信号通路的显著代表（p<0.02）：O-聚糖生物合成、细胞周期_Nek在细胞周期调节中的作用和免疫应答_干扰素的抗病毒作用。在外部临床基因组OVCA数据集（n=142）中，O-聚糖途径的表达与总生存率相关，与手术细胞减灭状态、分级和年龄无关（p<0.001）。细胞周期的表达水平_Nek在细胞周期调节和免疫应答中的作用_干扰素的抗病毒作用与存活率无关（分别为p=0.3107和p=0.5411）。总的来说，通过翻译后碳水化合物结合改变蛋白质功能的O-聚糖生物合成途径的表达与OVCA的总生存期独立相关。我们的研究结果揭示了OVCA对吉西他滨反应的分子基础，并确定了可能影响患者生存的信号通路。
Ovarian cancer (OVCA) is the most lethal gynecological malignancy. The high mortality rate associated with this disease is due in large part to the development of resistance to chemotherapy; however, the biological basis of this remains unclear. Gemcitabine is frequently used for the treatment of patients with platinum-resistant OVCA. We report molecular signaling pathways associated with OVCA response to gemcitabine. Forty-one OVCA cell lines were subjected to gene expression analysis; in parallel, IC50 values for gemcitabine were quantified using CellTiter-Blue viability assays. Pearson’s correlation coefficients were calculated for gene expression and gemcitabine IC50 values. The genes associated with gemcitabine sensitivity were subjected to pathway analysis. For the identified pathways, principal component analysis was used to derive pathway signatures and corresponding scores, which represent overall measures of pathway expression. Expression levels of the identified pathways were then evaluated in a series of clinico-genomic datasets from 142 patients with stage III/IV serous OVCA. We found that in vitro gemcitabine sensitivity was associated with expression of 131 genes (p<0.001). These genes include significant representation of three molecular signaling pathways (p<0.02): O-glycan biosynthesis, Cell cycle_Role of Nek in cell cycle regulation and Immune response_Antiviral actions of Interferons. In an external clinico-genomic OVCA dataset (n=142), expression of the O-glycan pathway was associated with overall survival, independent of surgical cytoreductive status, grade and age (p<0.001). Expression levels of Cell cycle_Role of Nek in cell cycle regulation and Immune response_Antiviral actions of Interferons were not associated with survival (p=0.3107 and p=0.5411, respectively). Collectively, expression of the O-glycan biosynthesis pathway, which modifies protein function via post-translational carbohydrate binding, is independently associated with overall survival from OVCA. Our findings shed light on the molecular basis of OVCA responsiveness to gemcitabine and also identify a signaling pathway that may influence patient survival.
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影响因子：
4.7
作者：
Gadducci, A;Sartori, E;Cristofani, R
通讯作者：
Cristofani, R
影响因子：
3.8
作者：
Chen, Dung-Tsa;Nasir, Aejaz;Culhane, Aedin;Venkataramu, Chinnambally;Fulp, William;Rubio, Renee;Wang, Tao;Agrawal, Deepak;McCarthy, Susan M.;Gruidl, Mike;Bloom, Gregory;Anderson, Tove;White, Joe;Quackenbush, John;Yeatman, Timothy
通讯作者：
Yeatman, Timothy
DOI：
10.1158/1078-0432.ccr-11-0735
发表时间：
2011-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Marchion DC;Cottrill HM;Xiong Y;Chen N;Bicaku E;Fulp WJ;Bansal N;Chon HS;Stickles XB;Kamath SG;Hakam A;Li L;Su D;Moreno C;Judson PL;Berchuck A;Wenham RM;Apte SM;Gonzalez-Bosquet J;Bloom GC;Eschrich SA;Sebti S;Chen DT;Lancaster JM
通讯作者：
Lancaster JM
DOI：
10.1093/jnci/86.20.1530
发表时间：
1994-10-19
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
LUND, B;HANSEN, OP;NEIJT, JP
通讯作者：
NEIJT, JP
影响因子：
4.7
作者：
Markman, M;Webster, K;Belinson, J
通讯作者：
Belinson, J