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Association between epithelial-mesenchymal transition and cancer stemness and their effect on the prognosis of lung adenocarcinoma


Abstract:
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, andP < 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.

Keywords:
Cancer stemness; CD133; epithelial-mesenchymal transition; lung adenocarcinoma; vimentin


Autoři: Terumasa Sowa 1;  Toshi Menju 1;  Makoto Sonobe 1;  Takao Nakanishi 1;  Kei Shikuma 1;  Naoto Imamura 1;  Hideki Motoyama 1;  Kyoko Hijiya 1;  Akihiro Aoyama 1;  Fengshi Chen 1;  Toshihiko Sato 1;  Masashi;  Kobayashi 2;  Akihiko Yoshizawa 3;  Hironori Haga 3;  Takashi Sozu 4;  Hiroshi Date 1
Působiště autorů: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan 1;  Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan 2;  Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan 3;  Department of Management Science, Faculty of Engineering, Tokyo University of Science, Tokyo, Japan 4
Vyšlo v časopise: Cancer Medicine 2015; Early View(Early View)
Kategorie: Original Research
prolekare.web.journal.doi_sk: https://doi.org/10.1002/cam4.556

© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
© 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Souhrn

Abstract:
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, andP < 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.

Keywords:
Cancer stemness; CD133; epithelial-mesenchymal transition; lung adenocarcinoma; vimentin


Zdroje

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