title: 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, 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.
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Terumasa
authors.initials: T
authors.lastname: Sowa
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toshi
authors.initials: T
authors.lastname: Menju
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Sonobe
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Nakanishi
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Shikuma
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Imamura
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Motoyama
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Hijiya
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Aoyama
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Fengshi
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Thoracic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshizawa
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
authors.affiliation: Department of Management Science, Faculty of Engineering, Tokyo University of Science, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sozu
authors.affiliation: Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Date
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers
keywords: CD133; Cancer stemness; epithelial-mesenchymal transition; lung adenocarcinoma; vimentin