title: Gli1 expression in cancer stem-like cells predicts poor prognosis in patients with lung squamous cell carcinoma.
abstract: Glioma-associated oncogene homolog 1 (Gli1) is involved in cancer stem cell (CSC) maintenance in various tumors; however, its expression and clinical significance in lung squamous cell carcinoma (LSCC) has not been reported. In this study, we aimed to reveal the clinical significance of Gli1 in LSCC and investigate the potential of Gli1 as a CSC marker by comparing its expression with that of other stemness-related genes in LSCC.
  
  
  
  We assessed the expressions of Gli1, LSD1, CD44, Sox9 and Sox2 by immunohistochemistry in the tissue specimens obtained from 101 patients with LSCC. The relationship of Gli1 expression with clinicopathological parameters and cell-cycle regulating genes was investigated.
  
  
  
  Gli1 expression was significantly correlated with T stage (P<0.001), lymph node metastasis (P=0.002), and clinical stage (P=0.005) of LSCC. The Kaplan-Meier survival analysis revealed that the expression of Gli1 in LSCC was all significantly associated with poor overall survival (OS: P=0.005). Cox regression analysis further confirmed that Gli1 is a prognostic marker of unfavorable clinical outcome of LSCC. Gli1 expression was significantly correlated with the expression of stemness-related genes such as LSD1 (P=0.009) and CD44 (P<0.001), but not with those of Sox2 and Sox9. However, Gli1 expression was associated with the expression of hypoxia-inducible factors1α (HIF1α; P<0.001) and Cyclin D1 (P=0.002), respectively. In additionally, microvessel density (MVD) was significantly higher in Gli1-positive LSCC than in the negative LSCC (P=0.026).
  
  
  
  Our results suggest that Gli1 may be a potential LSCC stem cell marker and an independent indicator of poor prognosis for patients with LSCC.
authors.affiliation: Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji 133002, China; Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, China.
authors.forename: Chun-Ai
authors.initials: CA
authors.lastname: Cui
authors.affiliation: Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji 133002, China; Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, China.
authors.forename: Zhao-Ting
authors.initials: ZT
authors.lastname: Yang
authors.affiliation: Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji 133002, China; Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Ni
authors.affiliation: Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji 133002, China; Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, China. Electronic address: jinyu@ybu.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Key Laboratory of Natural Resources of the Changbai Mountain and Functional Molecules, Ministry of Education, Yanbian University, Yanji 133002, China; Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji 133002, China. Electronic address: xuanyh1@ybu.edu.cn.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Xuan
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D011379:Prognosis; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; C497483:CD44 protein, human; C400551:GLI1 protein, human; D018960:Hyaluronan Receptors; C527782:SOX2 protein, human; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; D055748:SOXB1 Transcription Factors; D000071676:Zinc Finger Protein GLI1; D019938:Cyclin D1; D056466:Histone Demethylases; C495195:KDM1A protein, human
keywords: Cancer stem cell; Gli1; Lung squamous cell carcinoma; Prognosis