A 50-gene expression signature, with almost all of the genes involved in B-cell regulation, may predict relapse in stage I and stage II non–small cell lung cancers.

Favorable prognosis is associated with B-lymphocyte activity in patients with non–small cell lung cancer.

Even after successful surgical removal of tumors in stage I and stage II non–small cell lung cancers, more than half of patients relapse. Researchers from the Hospital Clinico San Carlos in Madrid, Spain, now have found a 50-gene expression signature that may predict which patients are most likely not to relapse.

Almost all of the 50 genes overexpressed in the signature are involved in B-cell regulation.

“What really determines the relapsing probability in early stage non–small cell lung cancer may not be in the tumor, but rather in the cross-talk with the patient's immune response,” says study co-leader and thoracic surgeon Florentino Hernando, MD, PhD, who presented the findings at the Third European Lung Cancer Conference in Geneva, Switzerland, on April 19.

The researchers followed 84 patients with stage I and stage II cancers after successful removal of all tumor matter. After 6 years, they correlated patient outcomes with RNA expression profiles of the tumors, using microarray technology and applying 41,000 different probes.

About one third of the patients exhibited the 50-gene expression pattern. These patients were only a third as likely to relapse as others in the study. A multicenter study of 162 patients has validated the 50-gene signature.

Further analysis showed that these genes specifically activate the immune response of B cells, regulating proliferation, extended lifespan, and cytotoxic action. “This isn't just a list of 50 genes,” says study co-leader and pathologist Julian Sanz, MD. “It represents a complex and integrated immune response.”

Because this gene signature suggests that a strong protective immune response may help prevent relapse, Sanz and Hernando speculate that postsurgical treatment with chemotherapy, which depletes the immune system, might interfere with that natural protection. They are now seeking collaborators to validate their findings and test this hypothesis.

The findings also suggest other research avenues. “A search for markers on the tumor surface that trigger the immune response could be a first step to developing a vaccine,” says Hernando.