机构：[1]Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China,[2]Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, United States of America,[3]Department of Oncology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China,[4]Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China,胸外科首都医科大学宣武医院[5]School of Life Sciences, Tsinghua University, Beijing 10084, China,[6]Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China,[7]Department of Pathology, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China
Background Squamous cell carcinomas (SCC) account for approximately 30% of non-small cell lung cancer (NSCLC). Current staging methods do not adequately predict outcome for this disease. EMX2 is a homeo-domain containing transcription factor known to regulate a key developmental pathway. This study assessed the significance of EMX2 as a prognostic and predictive marker for resectable lung SCC. Methods Two independent cohorts of patients with lung SCC undergoing surgical resection were studied. EMX2 protein expression was examined by immunohistochemistry, Western blot, or immunofluorescence. EMX2 expression levels in tissue specimens were scored and correlated with patient outcomes. Chemo-sensitivity of lung SCC cell lines stably transfected with EMX2 shRNAs to cisplatin, carboplatin, and docetaxel was examined in vitro. Results EMX2 expression was down-regulated in lung SCC tissue samples compared to their matched adjacent normal tissues. Positive EMX2 expression was significantly associated with improved overall survival in stage I lung SCC patients, and in stage II/IIIA lung SCC patients receiving adjuvant chemotherapy. EMX2 expression was also associated with expression of EMT markers in both lung SCC cell lines and tissue samples. Knock-down of EMX2 expression in lung SCC cells promoted chemo-resistance and cell migration. Conclusions EMX2 expression is down-regulated in lung SCC and its down-regulation is associated with chemo-resistance in lung SCC cells, possibly through regulation of Epithelial-to-Mesenchymal Transition (EMT). EMX2 may serve as a novel prognostic marker for stage I lung SCC patients and a prediction marker for stage II/IIIA lung SCC patients receiving adjuvant chemotherapy.
基金：
NIH/NCI (R01CA125030)
the Eileen D. Ludwig Endowed for Thoracic Oncology Research
The Bonnie J. Addario Lung Cancer Foundation,
the Kazan, McClain, Abrams, Fernandez, Lyons,Greenwood, Harley & Oberman Foundation,
the Barbara Isackson Lung Cancer Research Fund
the Key Program for Anti-cancer Research of Tianjin Municipal Science and Technology Commission (12ZCDZSY15400)
第一作者机构：[1]Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China,[2]Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, United States of America,
共同第一作者：
通讯作者：
通讯机构：[1]Department of Lung Cancer, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China,[2]Thoracic Oncology Program, Department of Surgery, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, United States of America,
推荐引用方式(GB/T 7714)：
Dongsheng Yue,Hui Li,Juanjuan Che,et al.EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas[J].PLOS ONE.2015,10(7):e0132134.doi:10.1371/journal.pone.0132134.
APA：
Dongsheng Yue,Hui Li,Juanjuan Che,Yi Zhang,Bhairavi Tolani...&Biao He.(2015).EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas.PLOS ONE,10,(7)
MLA：
Dongsheng Yue,et al."EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas".PLOS ONE 10..7(2015):e0132134
