PMID- 28286162 OWN - NLM STAT- MEDLINE DCOM- 20170809 LR - 20171212 IS - 1096-0945 (Electronic) IS - 0014-4800 (Linking) VI - 102 IP - 2 DP - 2017 Apr TI - Gli1 expression in cancer stem-like cells predicts poor prognosis in patients with lung squamous cell carcinoma. PG - 347-353 LID - S0014-4800(17)30017-5 [pii] LID - 10.1016/j.yexmp.2017.03.004 [doi] AB - PURPOSE: 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. METHODS: 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. RESULTS: 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 factors1alpha (HIF1alpha; 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). CONCLUSIONS: Our results suggest that Gli1 may be a potential LSCC stem cell marker and an independent indicator of poor prognosis for patients with LSCC. CI - Copyright (c) 2017. Published by Elsevier Inc. FAU - Cui, Yan AU - Cui Y AD - Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, China. FAU - Cui, Chun-Ai AU - Cui CA AD - 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. FAU - Yang, Zhao-Ting AU - Yang ZT AD - 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. FAU - Ni, Wei-Dong AU - Ni WD AD - 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. FAU - Jin, Yu AU - Jin Y AD - 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. FAU - Xuan, Yan-Hua AU - Xuan YH AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170309 PL - Netherlands TA - Exp Mol Pathol JT - Experimental and molecular pathology JID - 0370711 RN - 0 (Biomarkers, Tumor) RN - 0 (CCND1 protein, human) RN - 0 (CD44 protein, human) RN - 0 (GLI1 protein, human) RN - 0 (Hyaluronan Receptors) RN - 0 (SOX2 protein, human) RN - 0 (SOX9 Transcription Factor) RN - 0 (SOX9 protein, human) RN - 0 (SOXB1 Transcription Factors) RN - 0 (Zinc Finger Protein GLI1) RN - 136601-57-5 (Cyclin D1) RN - EC 1.14.11.- (Histone Demethylases) RN - EC 1.5.- (KDM1A protein, human) SB - IM MH - Aged MH - Biomarkers, Tumor MH - Carcinoma, Non-Small-Cell Lung/diagnosis/*genetics MH - Carcinoma, Squamous Cell/diagnosis/*genetics MH - Cyclin D1/genetics/metabolism MH - Female MH - *Gene Expression Regulation, Neoplastic MH - Histone Demethylases/genetics/metabolism MH - Humans MH - Hyaluronan Receptors/genetics/metabolism MH - Immunohistochemistry MH - Kaplan-Meier Estimate MH - Lung Neoplasms/diagnosis/*genetics MH - Male MH - Neoplastic Stem Cells/*metabolism MH - Prognosis MH - SOX9 Transcription Factor/genetics/metabolism MH - SOXB1 Transcription Factors/genetics/metabolism MH - Zinc Finger Protein GLI1/genetics/*metabolism OTO - NOTNLM OT - Cancer stem cell OT - Gli1 OT - Lung squamous cell carcinoma OT - Prognosis EDAT- 2017/03/14 06:00 MHDA- 2017/08/10 06:00 CRDT- 2017/03/14 06:00 PHST- 2017/01/16 00:00 [received] PHST- 2017/03/03 00:00 [revised] PHST- 2017/03/08 00:00 [accepted] PHST- 2017/03/14 06:00 [pubmed] PHST- 2017/08/10 06:00 [medline] PHST- 2017/03/14 06:00 [entrez] AID - S0014-4800(17)30017-5 [pii] AID - 10.1016/j.yexmp.2017.03.004 [doi] PST - ppublish SO - Exp Mol Pathol. 2017 Apr;102(2):347-353. doi: 10.1016/j.yexmp.2017.03.004. Epub 2017 Mar 9.