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

Our plain-English summary of The homeobox gene EMX2 is a prognostic and predictive marker in malignant pleural mesothelioma, by E. Giroux Leprieur, T. Hirata, M. Mo, et al (Lung Cancer, 2014).

The study

• Authors: E. Giroux Leprieur, T. Hirata, M. Mo, Z. Chen, J. Okamoto, G. Clement, H. Li, M. Wislez, D.M. Jablons, B. He
• Journal: Lung Cancer
• Published: 2014;85(3):465-71
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Objectives: 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.

Materials And 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.

Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

In plain English

This laboratory study used tumor tissue from 50 consecutive patients who had surgery for malignant pleural mesothelioma at the University of California, San Francisco, between 1999 and 2005. It did not study asbestos exposure. The authors measured the activity of a gene called EMX2 in each tumor and compared it with progression-free survival, meaning time without the disease getting worse. In 11 patients with paired samples, EMX2 was lower in tumor than in nearby normal tissue. EMX2 level was associated with tumor stage, and patients without a smoking history had higher EMX2. Median progression-free survival was 26.8 months in the high-EMX2 group versus 7.4 months in the low-EMX2 group (p = 0.001). The link with overall survival was only a trend. Among high-EMX2 patients, median progression-free survival was 17.7 months with chemotherapy before surgery versus 42.6 months without it (p = 0.054), above the study's 0.05 significance cutoff. The authors concluded that EMX2 may serve as a prognostic and predictive marker. They noted a modest sample size, possible overfitting of the cutoff, and a retrospective design.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective study of tumor specimens: EMX2 gene expression measured in surgically removed mesothelioma tissue and compared with patients' clinical outcomes
• Who was studied: 50 consecutive patients operated on for malignant pleural mesothelioma (MPM) at the University of California, San Francisco, 1999 to 2005 (41 men, 9 women; 42 epithelioid tumors). 24 received neoadjuvant chemotherapy before surgery. Paired normal tissue was available for 11 patients.
• Exposure: No asbestos or fiber exposure was studied. The factor examined was EMX2 mRNA expression in tumor tissue, measured by real-time PCR relative to pooled normal pleural tissue. Patients were split into high- and low-EMX2 groups using a cutoff chosen by the 'optimal p' approach.
• Main results:
  • In 11 patients with paired samples, EMX2 expression was significantly lower in tumor than in paired normal tissue (p = 0.005 by paired samples test, p = 0.004 by Wilcoxon signed rank test)
  • EMX2 expression was inversely correlated with IMIG stage (ANOVA, p less than 0.001)
  • Among 40 patients with known smoking status, those without a smoking history had higher EMX2 expression (p = 0.006)
  • Kaplan-Meier analysis, all patients: median progression-free survival was 26.8 months in the high-EMX2 group vs 7.4 months in the low-EMX2 group (p = 0.001)
  • Multivariate analysis: low EMX2 expression was associated with decreased progression-free survival (HR = 3.543, 95% CI 1.112 to 11.287)
  • Multivariate analysis: for overall survival, low EMX2 only trended toward worse outcome (HR = 2.617, 95% CI 0.974 to 7.035)
  • In stage I/II patients, median progression-free survival was 4.8 months with low EMX2 vs 26.8 months with high EMX2 (p less than 0.001)
  • Neoadjuvant chemotherapy, high-EMX2 patients: median progression-free survival was 17.7 months with chemotherapy vs 42.6 months without (p = 0.054)
  • Low-EMX2 patients had equivalent progression-free survival with and without neoadjuvant chemotherapy (13.8 vs 7.4 months, p = 0.572)
• The authors' conclusion: The authors concluded that EMX2 expression is downregulated in advanced cases of malignant pleural mesothelioma and may serve as a prognostic and predictive biomarker of progression-free survival. They also suggested that high-EMX2 patients may be unlikely to benefit from neoadjuvant chemotherapy.
• Limitations the authors state:
  • Modest sample size, due to the rarity of MPM, limited statistical power
  • Using the optimal p method to choose the cutoff may have caused overfitting, and there were no separate training and validation groups
  • Retrospective design: patients receiving neoadjuvant chemotherapy had different treatment regimens, which may have biased results

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Neoplasm, Prognosis, Tumorigenesis, IMIG, Progression-Free Survival, Multivariate Analysis, Neoadjuvant Chemotherapy.

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