title: Prognostic impact of cancer stem cell-related markers in non-small cell lung cancer patients treated with induction chemoradiotherapy.
abstract: The expression of several cancer stem cell (CSC)-related markers has been confirmed in non-small cell lung cancer (NSCLC). The aim of this study was to clarify the clinical role of CSC-related markers in patients with NSCLC undergoing induction chemoradiotherapy (CRT). Fifty patients with clinically diagnosed N2 or N3 NSCLC who underwent induction CRT with docetaxel and cisplatin concurrently with thoracic radiation followed by surgery were examined in this study. The expressions of CSC related markers (CD133, ALDH1, ABCG2, and Bmi-1) were examined using immunohistochemical staining in surgically resected specimens. Among the 50 patients, 20 patients had no residual tumor cells in the resected specimen when examined pathologically; CSC-related marker expressions and their correlation to survival were evaluated in the other 30 patients. After a median follow-up period of 72 months, the 5-year overall survival rate of the patients with CD133-positive or ALDH1-positive specimens was significantly worse than that of the patients with both CD133-negative and ALDH1-negative expressions (44.9% vs. 90.0%, respectively; P = 0.042). In a multivariate analysis, CD133 and ALDH1 negativity (P = 0.047) and cN2-3 single station metastasis (P = 0.03) were significant independent prognostic factors for prolonged survival. The expressions of CSC-related markers after CRT were significantly correlated with a poor prognosis in patients with NSCLC. The development of therapeutic strategies including adjuvant therapy that take CSC-related marker positivity into consideration is likely to be a key factor in further improvements of the prognosis of patients undergoing trimodality therapy.
authors.affiliation: Department of Cancer and Thoracic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shien
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Kouichi
authors.initials: K
authors.lastname: Ichimura
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Masashi
authors.initials: M
authors.lastname: Furukawa
authors.forename: Yuho
authors.initials: Y
authors.lastname: Maki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Muraoka
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Tanaka
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ueno
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Asano
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Masaomi
authors.initials: M
authors.lastname: Yamane
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oto
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kiura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Miyoshi
mesh_terms: D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000080924:Aldehyde Dehydrogenase 1 Family; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D060828:Induction Chemotherapy; D007527:Isoenzymes / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010455:Peptides / Q000378:metabolism; D063150:Polycomb Repressive Complex 1; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism
chemical_list: C116614:ABCG2 protein, human; D000071916:AC133 Antigen; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D015703:Antigens, CD; C069077:BMI1 protein, human; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D063150:Polycomb Repressive Complex 1