title: The homeobox gene EMX2 is a prognostic and predictive marker in malignant pleural mesothelioma.
abstract: OBJECTIVE
  Malignant pleural mesothelioma (MPM) is a highly aggressive neoplasm with a poor prognosis and limited treatment options. EMX2 is a homeobox transcription factor that may regulate key developmental pathways known to promote tumorigenesis. In this study, we evaluated the prognostic and predictive significance of EMX2 expression in MPM.
  
  
  METHODS
  Fifty surgically resected MPM specimens were studied. Quantitative real-time RT-PCR was used to analyze EMX2 mRNA expression. Association of EMX2 levels with clinical outcomes was evaluated with using the Kaplan-Meier method and a multivariate Cox proportional hazards regression model.
  
  
  RESULTS
  EMX2 expression was significantly associated with IMIG stage (p<0.001) and smoking history (p=0.006). Cox hazard regression modeling identified low-EMX2 expression as a negative prognostic factor in progression-free survival by both univariate (p=0.002) and multivariate analysis (p=0.002). Kaplan-Meier analysis revealed significant differences in progression-free survival between low- and high-EMX expressing groups in all patients (p=0.001), and also when grouped by early (I/II) stage disease (p<0.001), patients undergoing pleurectomy (p<0.001) and patients with an epitheliod subtype (p<0.004). Furthermore, EMX2 expression predicted response to neoadjuvant chemotherapy. High-EMX2 expression was associated with decreased progression-free survival after neoadjuvant therapy, suggesting that induction therapy should be avoided in these patients.
  
  
  CONCLUSIONS
  EMX2 expression is downregulated in advanced cases of malignant pleural mesothelioma and may serve as an important prognostic and predictive molecular biomarker of progression-free survival.
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, United States; Sorbonne Universities, UPMC Paris 6 University, GRC04 Theranoscan, F-75252 Paris, France; Respiratory Diseases and Thoracic Oncology Department, Ambroise Pare Hospital - APHP, Versailles Saint Quentin en Yvelines University, 9 avenue Charles de Gaulle, 92100 Boulogne-Billancourt, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Giroux Leprieur
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, United States; Department of Surgery, Division of Thoracic Surgery, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hirata
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing 10084, China.
authors.forename: Minli
authors.initials: M
authors.lastname: Mo
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, United States.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, United States; Department of Surgery, Division of Thoracic Surgery, Nippon Medical School, Tokyo 113-8602, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Okamoto
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, United States.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Clement
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, United States.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Sorbonne Universities, UPMC Paris 6 University, GRC04 Theranoscan, F-75252 Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Wislez
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, United States; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, United States.
authors.forename: David M
authors.initials: DM
authors.lastname: Jablons
authors.affiliation: Thoracic Oncology Program, Department of Surgery, University of California, San Francisco, San Francisco, CA 94115, United States; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, United States. Electronic address: biao.he@ucsfmedctr.org.
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D008297:Male; D008654:Mesothelioma / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D000086002:Mesothelioma, Malignant; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D015415:Biomarkers; D018398:Homeodomain Proteins; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins
keywords: EMX2; Mesothelioma; Neoadjuvant chemotherapy; Overall survival; Predictive marker; Prognosis; Progression-free survival