宫颈鳞状细胞癌中假定的干细胞标志物与不良临床预后相关。
Putative stem cell markers in cervical squamous cell carcinoma are correlated with poor clinical outcome.
作者信息
Hou Teng, Zhang Weijing, Tong Chongjie, Kazobinka Gallina, Huang Xin, Huang Yongwen, Zhang Yanna
机构信息
State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, GD, 510060, China.
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, HB, 430022, China.
出版信息
BMC Cancer. 2015 Oct 24;15:785. doi: 10.1186/s12885-015-1826-4.
BACKGROUND
The aim of this study was to elucidate the value of putative cancer stem cell markers Musashi-1, ALDH1, Sox2, and CD49f in predicting the prognosis in cervical squamous cell carcinoma (CSCC).
METHODS
Real-time PCR and immunohistochemistry staining was performed to examine Musashi-1, ALDH1, Sox2, and CD49f expression in archived specimens of CSCC patients with postoperative chemotherapy. Kaplan-Meier analysis and Cox proportional hazards model were used to assess the prognostic impact of CSC markers for overall survival (OS) and recurrent-free survival (RFS).
RESULTS
The Real-time PCR data showed that the expression of all markers were increased in CSCC tissues compared with in paired normal cervical tissues (P < 0.05). The IHC result showed that high expression of Msi1, ALDH1, Sox2, and CD49f was found in 25.7%, 43.0%, 62.0% and 29.0% CSCC samples, respectively. Moreover, high expression of Msi1 (P = 0.033 and P = 0.003, respectively), ALDH1 (P = 0.015 and P = 0.002, respectively), and Sox2 (P = 0.005 and P = 0.003, respectively), and low expression of CD49f (P = 0.027 and P = 0.025, respectively) were correlated with poor OS and PFS in CSCC patients. Interestingly, tumors with Msi1(high)/CD49f(low) expression had the poorest prognosis according to Msi1/CD49f stratification. In multivariate Cox regression analysis, Sox2 expression (P = 0.047 and P = 0.018, respectively), ALDH1 expression (P = 0.013 and P = 0.003, respectively), and CD49f expression (P = 0.008 and P = 0.003, respectively) were independent prognostic markers for both OS and RFS.
CONCLUSIONS
Our results suggest that cancer stem cell markers are linked with poor prognosis of CSCC patients.
背景
本研究旨在阐明假定的癌症干细胞标志物Musashi-1、醛脱氢酶1（ALDH1）、性别决定区Y框蛋白2（Sox2）和整合素α6（CD49f）在预测宫颈鳞状细胞癌（CSCC）预后中的价值。
方法
采用实时荧光定量聚合酶链反应（Real-time PCR）和免疫组织化学染色法检测接受术后化疗的CSCC患者存档标本中Musashi-1、ALDH1、Sox2和CD49f的表达。采用Kaplan-Meier分析和Cox比例风险模型评估癌症干细胞标志物对总生存期（OS）和无复发生存期（RFS）的预后影响。
结果
实时荧光定量聚合酶链反应数据显示，与配对的正常宫颈组织相比，所有标志物在CSCC组织中的表达均升高（P < 0.05）。免疫组织化学结果显示，Msi1、ALDH1、Sox2和CD49f高表达分别在25.7%、43.0%、62.0%和29.0%的CSCC样本中被发现。此外，Msi1高表达（分别为P = 0.033和P = 0.003）、ALDH1高表达（分别为P = 0.015和P = 0.002）和Sox2高表达（分别为P = 0.005和P = 0.003），以及CD49f低表达（分别为P = 0.027和P = 0.025）与CSCC患者较差的总生存期和无进展生存期相关。有趣的是，根据Msi1/CD49f分层，Msi1（高）/CD49f（低）表达的肿瘤预后最差。在多因素Cox回归分析中，Sox2表达（分别为P = 0.047和P = 0.018）、ALDH1表达（分别为P = 0.013和P = 0.003）和CD49f表达（分别为P = 0.008和P = 0.003）是总生存期和无复发生存期的独立预后标志物。
结论
我们的结果表明，癌症干细胞标志物与CSCC患者的不良预后相关。
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