A new genetic signature identified by Spanish researchers may provide robust and objective information about which patients with completely resected early stage non-small cell lung cancer are at low or high risk of relapse following surgery, according to Florentino Hernando, MD, who presented the findings at the 3rd European Lung Cancer Conference held recently in Geneva, Switzerland.
Dr. Hernando and a multidisciplinary team of investigators from Hospital Clinico San Carlos, Madrid, found a 50-gene predictor that appears to be capable of identifying which patients have the greatest risk of relapse. In a study of 84 patients with stage I and II non-small cell lung cancer, who had undergone surgery to remove their tumor, the gene signature accurately predicted which patients were at low risk of relapse.1
Low Risk of Relapse and Enhanced Immune Response
The researchers extracted RNA from frozen samples with more than 70% tumor cells. Tumors were analyzed using microarray expression. The data were normalized and subjected to unsupervised analysis to classify samples based on expression profiles. Association of identified molecular subgroups with clinical, pathologic, and molecular variables and disease-free survival was analyzed.
Following patients for 6 years, the researchers were able to correlate gene expression patterns with the clinical course of the disease, as well as the risk of relapse. They reported that the genes of the predictor were overexpressed in roughly one-third of the patients, all of whom had a low risk of relapse. Further analysis showed that these genes were related to the activity of B lymphocytes.
According to Dr. Florentino Hernando, the B cell-mediated immune response seems to have a very important role. The genetic profile identified by the researchers suggests that low-risk patients have an enhanced immune response against the tumor. Thus, treatments that may interfere with this response, such as postsurgical chemotherapy, must be reconsidered for the low-risk subgroup, according to investigators.
One-third of the patients showed an overexpression of an ‘immune’ genetic signature in their tumor specimens that was associated with better prognosis. The researchers concluded that expression of these 50 genes could make up a new genetic signature for non-small cell lung cancer and define subgroups of patients with different prognosis among those with completely resected early-stage NSCLC. ■
Disclosure: Dr. Hernando reported no potential conflict of interest.
Expert Point of View: David Carbone, MD, PhD
1. Hernando F, Sanz J, Jarabo JR, et al: A new genetic signature defining two prognostic groups among patiens with completely resected early non-small cell lung cancer. European Lung Cancer Conference, April 2012, Geneva, Switzerland. Abstract 2500.
Commenting on the study, David Carbone, MD, PhD, of the Vanderbilt-Ingram Cancer Center, said that the Spanish group studied tumors from patients with completely resected stage I and II NSCLC for gene RNA expression profiles using 41,000 different probes. “Since over one-half of these patients...