Association between epithelial-mesenchymal transition and cancer stemness and their effect on the prognosis of lung adenocarcinoma.
Association between epithelial-mesenchymal transition and cancer stemness and their effect on the prognosis of lung adenocarcinoma.
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DOI：
10.1002/cam4.556
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发表时间：
2015-12
期刊：
影响因子：
4
通讯作者：
Date, Hiroshi
中科院分区：
文献类型：
--
作者：
Sowa, Terumasa;Menju, Toshi;Sonobe, Makoto;Nakanishi, Takao;Shikuma, Kei;Imamura, Naoto;Motoyama, Hideki;Hijiya, Kyoko;Aoyama, Akihiro;Chen, Fengshi;Sato, Toshihiko;Kobayashi, Masashi;Yoshizawa, Akihiko;Haga, Hironori;Sozu, Takashi;Date, Hiroshi
据报道，上皮间质转化（EMT）和癌症干细胞（CS）是肺癌转移、复发和耐药性的关键现象；然而，它们在临床环境中对肿瘤恶性肿瘤的影响尚不完全清楚。这些因素之间的相互关联仍然难以捉摸，值得研究。本研究的目的是阐明 EMT 与 CS 之间的关联及其对肺腺癌患者预后的影响。收集2001年1月至2007年12月在京都大学医院接受手术的患者的肺腺癌标本共239例。通过肿瘤标本的免疫染色分析EMT（E-钙粘蛋白，波形蛋白）和CS（CD133，CD44，乙醛脱氢酶）标志物。对EMT与CS之间的关联以及患者的临床信息进行整合和统计分析。 E-钙粘蛋白、波形蛋白和 CD133 的分子表达与预后显着相关（P = 0.003、P = 0.005 和 P < 0.001）。 E-cadherin 与 vimentin 表达呈负相关（P < 0.001），而 vimentin 与 CD133 表达呈正相关（P = 0.020）。 CD133 是比 EMT 标记更强的预后因素。 CD133 表达升高是肺腺癌中 EMT 和 CS 关联的标志性标志。 EMT 和 CS 与肺腺癌相关。重要的是，CD133被认为是连接EMT和CS的关键因素，从而加剧肿瘤进展。
The epithelial‐mesenchymal transition (EMT) and cancer stemness (CS) are reported to be pivotal phenomena involved in metastasis, recurrence, and drug‐resistance in lung cancer; however, their effects on tumor malignancy in clinical settings are not completely understood. The mutual association between these factors also remains elusive and are worthy of investigation. The purpose of this study was to elucidate the association between EMT and CS, and their effect on the prognosis of patients with lung adenocarcinoma. A total of 239 lung adenocarcinoma specimens were collected from patients who had undergone surgery at Kyoto University Hospital from January 2001 to December 2007. Both EMT (E‐cadherin,vimentin) and CS (CD133, CD44, aldehyde dehydrogenase) markers were analyzed through immunostaining of tumor specimens. The association between EMT and CS as well as the patients' clinical information was integrated and statistically analyzed. The molecular expression of E‐cadherin, vimentin, and CD133 were significantly correlated with prognosis (P = 0.003, P = 0.005, and P < 0.001). A negative correlation was found between E‐cadherin and vimentin expression (P < 0.001), whereas, a positive correlation was found between vimentin and CD133 expression (P = 0.020). CD133 was a stronger prognostic factor than an EMT marker. Elevated CD133 expression is the signature marker of EMT and CS association in lung adenocarcinoma. EMT and CS are associated in lung adenocarcinoma. Importantly, CD133 is suggested to be the key factor that links EMT and CS, thereby exacerbating tumor progression.
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