The homeobox gene EMX2 is a prognostic and predictive marker in malignant pleural mesothelioma

•Low-EMX2 expression is a negative prognostic factor in mesothelioma.•High-EMX2 expression is associated with no benefice of neoadjuvant chemotherapy.•EMX2 expression is associated with IMIG stage and smoking history.

ObjectivesMalignant 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.Materials and methodsFifty 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.ResultsEMX2 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.ConclusionsEMX2 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.