Gene expression ratio test predicted postsurgical survival for mesothelioma

A four-gene expression ratio test conducted on tissue samples from patients undergoing surgery to treat mesothelioma predicted which patients had the best prognosis for survival.

The researchers prospectively examined three ratios of gene expression —TM4SF1:PKM2, TM4SF1:ARHGDIA and COBLL1:ARHGDIA — in 120 consecutive patients with malignant pleural mesothelioma. All patients underwent extrapleural pneumonectomy at Brigham and Women’s Hospital; 38 were still alive after a median follow-up of 15 months.

In previous research, the researchers “compared the differences in gene expression in tissue samples of malignant pleural mesothelioma stratified by patient outcome after surgical therapy and developed a gene ratio test that was calculated from the expression levels of four genes to predict patient outcome.” This study was designed to test the predictive value of this test.

The researchers stratified the patients into a good outcome group (58%) and a poor outcome group (42%) based on the results of the gene expression test. Median OS was 16.8 months for the good outcome group compared with 9.5 months for the poor outcome group (P<.001).

Median disease-specific survival for the good outcome group was 21.9 months vs. 15.9 months for the poor outcome group (P=.007).

Multivariate analysis showed that both lymph node status (HR=1.97; 95% CI, 1.15-3.38) and histological subtype (HR=1.88; 95% CI, 1.14-3.10) had significant prognostic power. The researchers concluded from those observations that the gene ratio test (HR=2.09 for death; 95% CI, 1.27-3.45) “appears to provide additional predictive information to current pathological staging methods.” – by Jason Harris

Gordon GJ. J Natl Cancer Inst. 2009;101:678-686.

Even though the test showed an independent predictive value on multivariate analysis, these results need to be duplicated by other groups who have more stringent selection criteria for surgery. Several groups across the country would not offer extrapleural pneumonectomy (EPP) to patients with sarcomatoid histology or N2 nodal status. Additionally, the patients determined by the four-gene expression ratio test to have better prognosis may do well regardless of EPP. To validate the claim that these patients will benefit from EPP will require a randomized trial comparing EPP plus chemotherapy with or without hemithoracic radiation vs. other less aggressive palliative surgical strategies plus chemotherapy.

– George Simon, MD

Director of the Thoracic Oncology Program
Fox Chase Cancer Center, Philadelphia