Identified gene variations associated with recurrence-free survival in NSCLC

Researchers have identified differences in genetic characteristics associated with age- and sex-specific patterns of increased and decreased five-year recurrence-free survival among patients with early stage non–small cell lung cancer.

The researchers examined the differences in the underlying biology of NSCLC based on patient age and sex in 787 patients diagnosed with early stage NSCLC between July 2008 and June 2009. Patients were divided into subgroups based on age (<70 years, n=520; or >70 years, n=267) and sex. Data were pooled from lung tumor samples with corresponding microarray data. Risk groups were defined by clusters based on the best (low-risk) or worst (high-risk) five-year recurrence-free survival.

When clusters of low-risk and high-risk patients aged younger than 70 years were compared, those who were at high risk had increased activation of the Src (25% vs. 6%; P<.001) and tumor necrosis factor (76% vs. 42%; P<.001) pathways. High-risk patients aged 70 years and older had increased activation of wound healing (40% vs. 24%; P=.02) and invasiveness (64% vs. 20%; P<.001) pathways when compared with low-risk patients.

Researchers next examined for sex-specific variations. When they compared 373 women and 414 men, data indicated that women had significantly better overall recurrence-free survival when compared with men (P=.008).

Women at high risk had increased activation of invasiveness (99% vs. 2%; P<.001) and signal transducer and activator of transcription 3 (STAT3) (72% vs. 35%; P<.001) pathways compared with those at low risk. Men at high risk had increased activation of STAT3 (87% vs. 18%; P<.001), tumor necrosis factor (90% vs. 46%; P<.001), epidermal growth factor receptor (13% vs. 2%; P=.003) and wound healing (50% vs. 22%; P<.001) pathways.

The researchers concluded that the findings “represent a novel approach to defining clinically relevant cohorts of NSCLC stratified by age and sex that are enriched for specific pathway activity and that would be more apt for therapeutic intervention when planning clinical trials with drugs that target specific pathway-related abnormalities or tumor biology.”

Mosterz W. JAMA. 2010;303:535-543.