HOXC10 Promotes the Metastasis of Human Lung Adenocarcinoma and Indicates Poor Survival Outcome.

HOXC10 Promotes the Metastasis of Human Lung Adenocarcinoma and Indicates Poor Survival Outcome.
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HOXC10促进人肺腺癌的转移并表明生存结果不佳

DOI:
10.3389/fphys.2017.00557
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发表时间:
2017
影响因子:
4
通讯作者:
Yuan CH
Yuan CH
中科院分区:
医学2区
文献类型:
--
作者:
Tang XL;Ding BX;Hua Y;Chen H;Wu T;Chen ZQ;Yuan CH

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背景资料:作为胚胎形态发生的主要调控因子,含同源结构域基因10(HOXC 10)已被发现促进人类癌症的进展,并指示较差的生存结果。然而,HOXC 10在肺腺癌中的作用尚不清楚。研究方法:在我们当地医院的63例原发性肺腺癌组织中评估了HOXC 10表达,并在来自6个GEO数据集(GSE 19188、GSE 31210、GSE 10072、GSE 7670、GSE 32863、GSE 30219)和Kaplan-Meier SPSS数据库的肺癌组织中进一步系统地证实了HOXC 10表达。HOXC 10在肺癌转移中的作用通过细胞和分子研究得到进一步证实。结果如下:HOXC 10在芜湖市第二人民医院肺腺癌组织中的表达显著增高,约为正常组织的4.219倍,且与TNM分期、淋巴结转移、远处转移显著相关。HOXC 10的上调表明芜湖市第二人民医院、GEO数据集和Kaplan-Meier生存数据库中肺癌患者的总体/无复发生存率较差,尤其是肺腺癌患者。敲除或异位表达实验证实HOXC 10可增强PI 3 K的磷酸化,调节上皮-间质转化(EMT)标志物MMP 2/9、VCAM-1、vimentin和E-cadherin的表达。细胞研究进一步证实HOXC 10是肺癌细胞迁移、侵袭和粘附所必需的。结论:这些发现表明HOXC 10在人肺癌的转移中起着关键作用,并突出了其作为人肺腺癌的潜在预后标志物或治疗靶点的有用性。
Background: As master regulator of embryonic morphogenesis, homeodomain-containing gene 10 (HOXC10) has been found to promote progression of human cancers and indicates poor survival outcome. However, the role of HOXC10 in lung adenocarcinoma still unclear. Methods: HOXC10 expression was evaluated in 63 primary lung adenocarcinoma tissues from our local hospital, and further systematically confirmed in lung cancer tissues from six GEO datasets (GSE19188, GSE31210, GSE10072, GSE7670, GSE32863, GSE30219), and Kaplan-Meier plotter database. The role of HOXC10 in lung cancer metastasis was further validated by cellular and molecular studies. Results: The expression of HOXC10 was significantly increased in human lung adenocarcinoma samples from Wuhu No.2 People's Hospital, about 4.219 times compared with normal tissues, and significantly correlated with TNM stage, lymph node, and distal metastasis. Upregulation of HOXC10 indicated a poor overall/relapse free survival of lung cancer patients from Wuhu No.2 People's Hospital, GEO datasets, and Kaplan-Meier plotter database, especially in patients with lung adenocarcinoma. Knockdown or ectopic expression assays confirmed that HOXC10 enhanced the phosphorylation of PI3K, regulated the expression of epithelial-to-mesenchymal transition (EMT) markers: MMP2/9, VCAM-1, vimentin and E-cadherin. Cellular study further confirmed that HOXC10 was required for migration, invasion and adhesion of lung cancer cells. Conclusion: These findings suggest that HOXC10 plays a pivotal role in the metastasis of human lung cancer and highlight its usefulness as a potential prognostic marker or therapeutic target in human lung adenocarcinoma.
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