Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways.
Characterization of single disseminated prostate cancer cells reveals tumor cell heterogeneity and identifies dormancy associated pathways.
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DOI：
10.18632/oncotarget.2480
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发表时间：
2014-10-30
期刊：
影响因子：
--
通讯作者：
Morrissey C
中科院分区：
文献类型：
--
作者：
Chéry L;Lam HM;Coleman I;Lakely B;Coleman R;Larson S;Aguirre-Ghiso JA;Xia J;Gulati R;Nelson PS;Montgomery B;Lange P;Snyder LA;Vessella RL;Morrissey C
癌症休眠是指从原发肿瘤切除到复发之间延长的临床无病时间，常见于前列腺癌（PCa）、乳腺癌、食管癌和其他癌症。在无疾病证据（NED）和晚期疾病（ADV）的患者中均检测到PCa播散性肿瘤细胞（DTC）。然而，DTC的分子和细胞性质是未知的。我们在癌症患者中进行了首次单DTC转录组学分析的现场研究，以确定与癌症休眠相关的分子特征。我们分析了来自NED或ADV PCa患者骨髓的85个EpCAM+/CD 45 −细胞。我们分析了44个具有高前列腺上皮特征的DTC，并排除了41个具有高红细胞特征和低前列腺上皮特征的细胞。DTC可分为3组：NED、ADV_1和ADV_2，其中ADV_1组呈现与p38应激激活激酶途径相关的不同基因表达模式。此外，来自NED组的DTC富含与头颈部鳞状细胞癌和乳腺癌相关的肿瘤休眠特征。这项研究提供了p38通路作为早期复发的潜在生物标志物和治疗干预的有吸引力的靶点的第一个临床证据。
Cancer dormancy refers to the prolonged clinical disease-free time between removal of the primary tumor and recurrence, which is common in prostate cancer (PCa), breast cancer, esophageal cancer, and other cancers. PCa disseminated tumor cells (DTC) are detected in both patients with no evidence of disease (NED) and advanced disease (ADV). However, the molecular and cellular nature of DTC is unknown. We performed a first-in-field study of single DTC transcriptomic analyses in cancer patients to identify a molecular signature associated with cancer dormancy. We profiled eighty-five individual EpCAM+/CD45− cells from the bone marrow of PCa patients with NED or ADV. We analyzed 44 DTC with high prostate-epithelial signatures, and eliminated 41 cells with high erythroid signatures and low prostate epithelial signatures. DTC were clustered into 3 groups: NED, ADV_1, and ADV_2, in which the ADV_1 group presented a distinct gene expression pattern associated with the p38 stress activated kinase pathway. Additionally, DTC from the NED group were enriched for a tumor dormancy signature associated with head and neck squamous carcinoma and breast cancer. This study provides the first clinical evidence of the p38 pathway as a potential biomarker for early recurrence and an attractive target for therapeutic intervention.
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影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
2.6
作者：
Lammers, R;Giesert, C;Bühring, HJ
通讯作者：
Bühring, HJ
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影响因子：
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作者：
Morrissey, Colm;Roudier, Martine P.;Dowell, Alex;True, Lawrence D.;Ketchanji, Melanie;Welty, Christopher;Corey, Eva;Lange, Paul H.;Higano, Celestia S.;Vessella, Robert L.
通讯作者：
Vessella, Robert L.
影响因子：
10.3
作者：
Marshall, Jean-Claude A.;Collins, Joshua W.;Steeg, Patricia S.
通讯作者：
Steeg, Patricia S.