Cui Yan, Cui Chun-Ai, Yang Zhao-Ting, Ni Wei-Dong, Jin Yu, Xuan Yan-Hua
Department of Oncology, Affiliated Hospital of Yanbian University, Yanji, China.
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.
Exp Mol Pathol. 2017 Apr;102(2):347-353. doi: 10.1016/j.yexmp.2017.03.004. Epub 2017 Mar 9.
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.
胶质瘤相关癌基因同源物1（Gli1）参与多种肿瘤中癌症干细胞（CSC）的维持；然而，其在肺鳞状细胞癌（LSCC）中的表达及临床意义尚未见报道。在本研究中，我们旨在揭示Gli1在LSCC中的临床意义，并通过比较其与LSCC中其他干性相关基因的表达，研究Gli1作为CSC标志物的潜力。
我们采用免疫组织化学方法评估了101例LSCC患者组织标本中Gli1、LSD1、CD44、Sox9和Sox2的表达。研究了Gli1表达与临床病理参数及细胞周期调控基因的关系。
Gli1表达与LSCC的T分期（P<0.001）、淋巴结转移（P=0.002）及临床分期（P=0.005）显著相关。Kaplan-Meier生存分析显示，LSCC中Gli1的表达均与总体生存率差显著相关（总生存期：P=0.005）。Cox回归分析进一步证实，Gli1是LSCC不良临床结局的预后标志物。Gli1表达与LSD1（P=0.009）和CD44（P<0.001）等干性相关基因的表达显著相关，但与Sox2和Sox9的表达无关。然而，Gli1表达分别与缺氧诱导因子1α（HIF1α；P<0.001）和细胞周期蛋白D1（P=0.002）的表达相关。此外，Gli-1阳性的LSCC微血管密度（MVD）显著高于阴性LSCC（P=0.026）。
我们的结果表明，Gli1可能是潜在的LSCC干细胞标志物，也是LSCC患者预后不良的独立指标。
