Gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer.
Gene expression data reveal common pathways that characterize the unifocal nature of ovarian cancer.
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DOI：
10.1016/j.ajog.2013.08.004
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发表时间：
2013-12
影响因子：
9.8
通讯作者：
Lancaster, Johnathan M.
中科院分区：
文献类型：
--
作者：
Marchion, Douglas C.;Xiong, Yin;Chon, Hye Sook;Al Sawah, Entidhar;Zgheib, Nadim Bou;Ramirez, Ingrid J.;Abbasi, Forough;Stickles, Xiaomang B.;Judson, Patricia L.;Hakam, Ardeshir;Gonzalez-Bosquet, Jesus;Wenham, Robert M.;Apte, Sachin M.;Berglund, Anders E.;Lancaster, Johnathan M.
评估卵巢癌 (OVCA) 筛查和早期检测工作的生物学有效性，并表征与人类癌症转移和患者生存相关的信号通路。使用全基因组表达谱和 DNA 测序，我们比较了 30 名晚期 OVCA 患者的盆腔和匹配的盆腔外植入物的分子信号通路和 p53 基因突变的表达。在来自 389 名卵巢癌、前列腺癌和口腔癌患者的一系列原发性或早期癌症样本与转移性或复发性癌症样本中进一步评估了差异表达途径。还在来自 1,691 名卵巢癌、乳腺癌、结肠癌、脑癌、肺癌和白血病患者的 9 个独立临床基因组数据集中评估了转移途径与生存的关联。研究了一种途径 (TGF-WNT) 对体外 OVCA 细胞迁移的抑制作用。盆腔和盆腔外 OVCA 植入物表现出相似的信号通路表达模式和相同的 p53 突变。然而，我们发现了 3 种分子途径/细胞过程，这些途径/细胞过程在盆腔和盆腔外 OVCA 样本之间以及原发/早期和转移/晚期或复发性卵巢癌、口腔癌和前列腺癌之间存在差异表达。此外，它们的表达与卵巢癌（P=0.006）、结肠癌（P=0.005）和白血病（P=0.05）的总生存率相关。青蒿琥酯诱导的 TGF-WNT 通路抑制损害了 OVCA 细胞迁移。晚期 OVCA 起源于骨盆，支持早期检测/筛查工作的有效性。与盆腔外 OVCA 扩散相关的分子途径也与其他人类癌症的转移以及患者的总体生存率相关。这些途径代表了转移性疾病患者有吸引力的治疗靶点。
To evaluate the biologic validity of ovarian cancer (OVCA) screening and early detection efforts and to characterize signaling pathways associated with human cancer metastasis and patient survival. Using genome-wide expression profiling and DNA sequencing, we compared pelvic and matched extra-pelvic implants from 30 patients with advanced-stage OVCA for expression of molecular signaling pathways and p53 gene mutations. Differentially expressed pathways were further evaluated in a series of primary or early-stage versus metastatic or recurrent cancer samples from 389 ovarian, prostate, and oral cancer patients. Metastasis pathways were also evaluated for associations with survival in nine independent clinico-genomic datasets from 1,691 ovarian, breast, colon, brain, and lung cancer and leukemia patients. The inhibitory effects of one pathway (TGF-WNT) on in-vitro OVCA cell migration were studied. Pelvic and extra-pelvic OVCA implants demonstrated similar patterns of signaling pathway expression and identical p53 mutations. However, we identified 3 molecular pathways/cellular processes that were differentially expressed between pelvic and extra-pelvic OVCA samples and between primary/early-stage and metastatic/advanced or recurrent ovarian, oral, and prostate cancers. Furthermore, their expression was associated with overall survival from ovarian cancer (P=0.006), colon cancer (1 pathway at P=0.005), and leukemia (P=0.05). Artesunate-induced TGF-WNT pathway inhibition impaired OVCA cell migration. Advanced-stage OVCA has a unifocal origin in the pelvis, supporting validity of early detection/screening efforts. Molecular pathways associated with extra-pelvic OVCA spread are also associated with metastasis from other human cancers and with overall patient survival. Such pathways represent appealing therapeutic targets for patients with metastatic disease.
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脊椎动物神经发育和功能中的Wnt信号传导。
影响因子：
6.2
作者：
Mulligan, Kimberly A.;Cheyette, Benjamin N. R.
通讯作者：
Cheyette, Benjamin N. R.
影响因子：
6.4
作者：
Khalique, Lalarukh;Ayhan, Ayse;Ramus, Susan J.
通讯作者：
Ramus, Susan J.
DOI：
10.1093/jnci/84.23.1793
发表时间：
1992-12-02
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
JACOBS, IJ;KOHLER, MF;BAST, RC
通讯作者：
BAST, RC
影响因子：
4.4
作者：
Semba, S;Kusumi, R;Sasano, H
通讯作者：
Sasano, H
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