Reduced Gene Expression Indicative of Mesothelioma Cell Death and Response to Treatment
May 24, 2011
Although mesothelioma can be difficult to treat, for patients with early-stage cancer certain therapies may effectively reduce their tumors. To help predict a mesothelioma patient’s potential response to treatment, a recent study examined the expression levels of four unique genes that appear to be involved in mesothelioma development.
The genes included in the study were PKM2, ARHGDIA, COBLL1 and TM4SF1. These genes have been previously studied in prognostic tests performed on a malignant pleural mesothelioma patient.
The latter three genes have each been found to indicate a patient’s mortality risk and receptiveness to mesothelioma treatment by monitoring programmed cell death. Previous studies of TM4SF1 have also indicated that it may be linked to metastasis.
When ARHGDIA, COBLL1 and M4SF1 were expressed in lower concentrations, apoptosis (natural death of cancerous cells) was found to be elevated. The in vitro (Latin for “within glass,” indicating in a test tube) study showed that a decreased level of these genes in cultured cells was correlated with two- to four-fold increase in apoptosis.
Reduction of PKM2 was not shown to correlate with apoptosis or mitosis. Other experimental genes were considered, yet none provided a significant increase in apoptosis.
Mitosis, or cellular division, was also studied in correlation with the expression levels of these four genes. No mitosis-related changes were noted after knockdown (reduction) of any of the experimental genes. However, increased apoptosis led to modest but significant reduction in cancerous cells.
Researchers concluded that reduced expression of these genes in tumor cells prevents cells from dying and promotes cell survival. This test is thought to help doctors determine which patients would be least receptive to chemotherapy or radiation. Overall, TM4SF1 and COBLL1 are primarily associated with good prognosis while ARHGDIA is often a marker of poor prognosis. As a result, this test could help doctors tailor a patient’s therapy regimen to include the treatments that would be met with the least resistance.