title: EMX2 Is a Predictive Marker for Adjuvant Chemotherapy in Lung Squamous Cell Carcinomas.
abstract: 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.
authors.affiliation: 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; 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.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Yue
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Oncology, Beijing Friendship Hospital of Capital Medical University, Beijing 100050, China.
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Che
authors.affiliation: Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Bhairavi
authors.initials: B
authors.lastname: Tolani
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 10084, China.
authors.forename: Minli
authors.initials: M
authors.lastname: Mo
authors.affiliation: 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.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 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; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
authors.forename: Runfen
authors.initials: R
authors.lastname: Cheng
authors.affiliation: 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.
authors.forename: Joy Q
authors.initials: JQ
authors.lastname: Jin
authors.affiliation: 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.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Luh
authors.affiliation: 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.
authors.forename: Cathryn
authors.initials: C
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Hsin-Hui K
authors.initials: HH
authors.lastname: Tseng
authors.affiliation: 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.
authors.forename: Etienne
authors.initials: E
authors.lastname: Giroux-Leprieur
authors.affiliation: 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.
authors.forename: Gavitt A
authors.initials: GA
authors.lastname: Woodard
authors.affiliation: 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.
authors.forename: Xishan
authors.initials: X
authors.lastname: Hao
authors.affiliation: 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.
authors.forename: Changli
authors.initials: C
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
authors.affiliation: 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.
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002465:Cell Movement; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015536:Down-Regulation; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008168:Lung / Q000737:chemistry; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage; D011013:Pneumonectomy; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077235:Vinorelbine; D000093542:Gemcitabine; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D003841:Deoxycytidine; D004317:Doxorubicin; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D009944:Organoplatinum Compounds; D017239:Paclitaxel; D034741:RNA, Small Interfering; D014157:Transcription Factors; D014747:Vinblastine; D000077235:Vinorelbine; D000093542:Gemcitabine; D000099260:Empty Spiracles Homeobox Proteins